Skip to main content

Advertisement

SpringerLink
Log in

Targeting epigenetic deregulations for the management of esophageal carcinoma: recent advances and emerging approaches

  • Review
  • Published:
Cell Biology and Toxicology Aims and scope Submit manuscript

Abstract

Ranking from seventh in incidence to sixth in mortality, esophageal carcinoma is considered a severe malignancy of food pipe. Later-stage diagnosis, drug resistance, and a high mortality rate contribute to its lethality. Esophageal squamous cell carcinoma and esophageal adenocarcinoma are the two main histological subtypes of esophageal carcinoma, with squamous cell carcinoma alone accounting for more than eighty percent of its cases. While genetic anomalies are well known in esophageal cancer, accountability of epigenetic deregulations is also being explored for the recent two decades. DNA methylation, histone modifications, and functional non-coding RNAs are the crucial epigenetic players involved in the modulation of different malignancies, including esophageal carcinoma. Targeting these epigenetic aberrations will provide new insights into the development of biomarker tools for risk stratification, early diagnosis, and effective therapeutic intervention. This review discusses different epigenetic alterations, emphasizing the most significant developments in esophageal cancer epigenetics and their potential implication for the detection, prognosis, and treatment of esophageal carcinoma. Further, the preclinical and clinical status of various epigenetic drugs has also been reviewed.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data Availability

Not applicable.

Abbreviations

3-MA:

3-Methyladenine

ASOs:

Antisense oligonucleotides

BET:

Bromodomain and extra terminal domain

BRDi:

Bromodomain inhibitors

BRDs:

Bromodomains

BRDT:

Bromodomain testis-specific protein

circRNAs:

Circular RNAs

DEGs:

Differentially expressed genes

DNMT:

DNA methyltransferase

DNMTis:

DNA methyltransferase inhibitors

EAC:

Esophageal adenocarcinoma

EC:

Esophageal cancer

ESCC:

Esophageal squamous cell carcinoma

EZH2:

Enhancer of Zeste Homolog 2

GLI:

Glioma-associated oncogene homolog

HATs:

Histone acetyltransferases

HDACis:

Histone deacetylase inhibitors

HDACs:

Histone deacetylases

HDMs:

Histone demethylases

HMTs:

Histone methyltransferases

LINEs:

Long interspersed transposable elements

lncRNAs:

Long non-coding RNAs

MDM2:

Murine double min 2

miRNAs:

MicroRNAs

ncRNA:

Non-coding RNA

PD1:

Programmed death-1

PD-L1:

Programmed death ligand-1

PROTAC:

Proteolysis-targeting chimeric

RNAi:

RNA-mediated interference

scATAC-seq:

Transposase-accessible chromatin sequencing assay at the single-cell level

SINEs :

Short interspersed transposable elements

siRNA :

Short interfering RNAs

TME:

Tumor microenvironment

TSGs:

Tumor suppressor genes

YAP1:

Yes-associated protein 1.

References

  • Ahrens TD, Werner M, Lassmann S. Epigenetics in esophageal cancers. Cell Tissue Res. 2014;356:643–55.

    Article  PubMed  CAS  Google Scholar 

  • Ahrens TD, Timme S, Hoeppner J, Ostendorp J, Hembach S, Follo M, et al. Selective inhibition of esophageal cancer cells by combination of HDAC inhibitors and azacytidine. Epigenetics. 2015;10(5):431–45.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ahuja N, Sharma AR, Baylin SB. Epigenetic therapeutics: a new weapon in the war against cancer. Ann Rev Med. 2016;67:73–89.

    Article  PubMed  CAS  Google Scholar 

  • Alvarez-Trotta A, Wang Z, Shersher E, Li B, Long J, Lohse I, et al. The bromodomain inhibitor IBET-151 attenuates vismodegib-resistant esophageal adenocarcinoma growth through reduction of GLI signaling. Oncotarget. 2020;11(33):3174.

    Article  PubMed  PubMed Central  Google Scholar 

  • An J, Ko M. Epigenetic modification of cytosines in hematopoietic differentiation and malignant transformation. Int J Mol Sci. 2023;24(2):1727.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Asadi M, Shanehbandi D, Mohammadpour H, Hashemzadeh S, Sepehri B. Expression level of miR-34a in tumor tissue from patients with esophageal squamous cell carcinoma. J Gastr Cancer. 2019;50:304–7.

    Article  CAS  Google Scholar 

  • Ashwal-Fluss R, Meyer M, Pamudurti NR, Ivanov A, Bartok O, Hanan M, et al. circRNA biogenesis competes with pre-mRNA splicing. Mol Cell. 2014;56(1):55–66.

    Article  PubMed  CAS  Google Scholar 

  • Baba Y, Watanabe M, Baba H. A review of the alterations in DNA methylation in esophageal squamous cell carcinoma. Surg Today. 2013;43:1355–64.

    Article  PubMed  CAS  Google Scholar 

  • Baba Y, Murata A, Watanabe M, Baba H. Clinical implications of the LINE-1 methylation levels in patients with gastrointestinal cancer. Surg Today. 2014;44(10):1807–16.

    Article  PubMed  CAS  Google Scholar 

  • Baba Y, Ishimoto T, Kurashige J, Iwatsuki M, Sakamoto Y, Yoshida N, et al. Epigenetic field cancerization in gastrointestinal cancers. Cancer Lett. 2016;375(2):360–6.

    Article  PubMed  CAS  Google Scholar 

  • Bannister AJ, Kouzarides T. Regulation of chromatin by histone modifications. Cell Res. 2011;21(3):381–95.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Barbarotta L, Hurley K. Romidepsin for the treatment of peripheral T-cell lymphoma. J Adv Pract Oncol. 2015;6(1):22.

    PubMed  PubMed Central  Google Scholar 

  • Baylin SB, Herman JG. DNA hypermethylation in tumorigenesis: epigenetics joins genetics. Trends Gene. 2000;16(4):168–74.

    Article  CAS  Google Scholar 

  • Baylin SB, Jones PA. A decade of exploring the cancer epigenome—biological and translational implications. Nat Rev Cancer. 2011;11(10):726–34.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Baylin SB, Jones PA. Epigenetic determinants of cancer. Cold Spring Harbor Persp Biol. 2016;8(9):a019505.

    Article  Google Scholar 

  • Berdasco M, Esteller M. Clinical epigenetics: seizing opportunities for translation. Nat Rev Gene. 2019;20(2):109–27.

    Article  CAS  Google Scholar 

  • Bevill SM, Olivares-Quintero JF, Sciaky N, Golitz BT, Singh D, Beltran AS, et al. GSK2801, a BAZ2/BRD9 bromodomain inhibitor, synergizes with BET inhibitors to induce apoptosis in triple-negative breast cancer BAZ2A/B regulate BRD2 chromatin function. Mol Cancer Res. 2019;17(7):1503–18.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bian YS, Osterheld MC, Fontolliet C, Bosman FT, Benhattar J. p16 inactivation by methylation of the CDKN2A promoter occurs early during neoplastic progression in Barrett's esophagus. Gastroenterology. 2002;122(4):1113–21.

    Article  PubMed  CAS  Google Scholar 

  • Biswas S, Rao CM. Epigenetics in cancer: fundamentals and beyond. Pharmacol Therap. 2017;173:118–34.

    Article  CAS  Google Scholar 

  • Biswas S, Rao CM. Epigenetic tools (The Writers, The Readers and The Erasers) and their implications in cancer therapy. Eur J Pharmacol. 2018;837:8–24.

    Article  PubMed  CAS  Google Scholar 

  • Black JC, Van Rechem C, Whetstine JR. Histone lysine methylation dynamics: establishment, regulation, and biological impact. Mol Cell. 2012;48(4):491–507.

    Article  PubMed  CAS  Google Scholar 

  • Bouyahya A, Mechchate H, Oumeslakht L, Zeouk I, Aboulaghras S, Balahbib A, et al. The role of epigenetic modifications in human cancers and the use of natural compounds as epidrugs: Mechanistic pathways and pharmacodynamic actions. Biomolecules. 2022;12(3):367.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Brueckner B, Garcia Boy R, Siedlecki P, Musch T, Kliem HC, Zielenkiewicz P, et al. Epigenetic reactivation of tumor suppressor genes by a novel small-molecule inhibitor of human DNA methyltransferases. Cancer Res. 2005;65(14):6305–11.

    Article  PubMed  CAS  Google Scholar 

  • Campbell P, Thomas CM. Belinostat for the treatment of relapsed or refractory peripheral T-cell lymphoma. J Oncol Pharm Pract. 2017;23(2):143–7.

    Article  PubMed  CAS  Google Scholar 

  • Cao J, Yan Q. Cancer epigenetics, tumor immunity, and immunotherapy. Trends Cancer. 2020;6(7):580–92.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cao P, Jin Q, Feng L, Li H, Qin G, Zhou G. Emerging roles and potential clinical applications of noncoding RNAs in hepatocellular carcinoma. In: Seminars in Cancer Biology, vol. 75. Academic Press; 2021. p. 136–52.

    Google Scholar 

  • Casado-Pelaez M, Bueno-Costa A, Esteller M. Single cell cancer epigenetics. Trends in Cancer. 2022.

  • Castillo-Aguilera O, Depreux P, Halby L, Arimondo PB, Goossens L. DNA methylation targeting: the DNMT/HMT crosstalk challenge. Biomolecules. 2017;7(1):3.

    Article  PubMed  PubMed Central  Google Scholar 

  • Cavalli G, Heard E. Advances in epigenetics link genetics to the environment and disease. Nature. 2019;571(7766):489–99.

    Article  PubMed  CAS  Google Scholar 

  • Chang WL, Hsieh CH, Kuo IY, Lin CH, Huang YL, Wang YC. Nutlin-3 acts as a DNA methyltransferase inhibitor to sensitize esophageal cancer to chemoradiation. Mol Carcinogen. 2022;62(2):277.

    Article  Google Scholar 

  • Chen LL, Yang L. Regulation of circRNA biogenesis. RNA Biol. 2015;12(4):381–8.

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen M, Nie J, Liu Y, Li X, Zhang Y, Brock MV, et al. Phase Ib/II study of safety and efficacy of low-dose decitabine-primed chemoimmunotherapy in patients with drug-resistant relapsed/refractory alimentary tract cancer. Int J Cancer. 2018;143(6):1530–40.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chen X, Sun H, Zhao Y, Zhang J, Xiong G, Cui Y, Lei C. CircRNA circ_0004370 promotes cell proliferation, migration, and invasion and inhibits cell apoptosis of esophageal cancer via miR-1301-3p/COL1A1 axis. Open Med. 2021;16(1):104–16.

    Article  Google Scholar 

  • Cheng YW, Liao LD, Yang Q, Chen Y, Nie PJ, Zhang XJ, et al. The histone deacetylase inhibitor panobinostat exerts anticancer effects on esophageal squamous cell carcinoma cells by inducing cell cycle arrest. Cell Biochem Funct. 2018;36(8):398–407.

    Article  PubMed  CAS  Google Scholar 

  • Cheng Y, He C, Wang M, Ma X, Mo F, Yang S, et al. Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials. Signal Trans Target Therap. 2019;4(1):62.

    Article  Google Scholar 

  • Cheng W, Shi X, Lin M, Yao Q, Ma J, Li J. LncRNA MAGI2-AS3 overexpression sensitizes esophageal cancer cells to irradiation through down-regulation of HOXB7 via EZH2. Front Cell Dev Biol. 2020;8:552822.

    Article  PubMed  PubMed Central  Google Scholar 

  • Clegg MA, Bamborough P, Chung CW, Craggs PD, Gordon L, Grandi P, et al. Application of atypical acetyl-lysine methyl mimetics in the development of selective inhibitors of the bromodomain-containing protein 7 (BRD7)/bromodomain-containing protein 9 (BRD9) bromodomains. J Med Chem. 2020;63(11):5816–40.

    Article  PubMed  CAS  Google Scholar 

  • Clément G, Braunschweig R, Pasquier N, Bosman FT, Benhattar J. Methylation of APC, TIMP3, and TERT: a new predictive marker to distinguish Barrett's oesophagus patients at risk for malignant transformation. J Pathol: J Pathol Soc Great Br Ireland. 2006;208(1):100–7.

    Article  Google Scholar 

  • Cohen P. The structure and regulation of protein phosphatases. Ann Rev Biochem. 1989;58(1):453–508.

    Article  PubMed  CAS  Google Scholar 

  • Connolly RM, Li H, Jankowitz RC, Zhang Z, Rudek MA, Jeter SC, et al. Combination epigenetic therapy in advanced breast cancer with 5-azacitidine and entinostat: a Phase II National Cancer Institute/Stand Up to Cancer Study Phase II Study 5-azacitidine and entinostat in breast cancer. Clin Cancer Res. 2017;23(11):2691–701.

    Article  PubMed  CAS  Google Scholar 

  • Cossío FP, Esteller M, Berdasco M. Towards a more precise therapy in cancer: exploring epigenetic complexity. Curr Opin Chem Biol. 2020;57:41–9.

    Article  PubMed  Google Scholar 

  • Cui G, Liu D, Li W, Li Y, Liang Y, Shi W, Zhao S. miR-194 inhibits proliferation and invasion and promotes apoptosis by targeting KDM5B in esophageal squamous cell carcinoma cells. Exp Biol Med. 2017;242(1):45–52.

    Article  CAS  Google Scholar 

  • Cui Y, Zhang C, Lian H, Xie L, Xue J, Yin N, Guan F. LncRNA linc00460 sponges miR-1224-5p to promote esophageal cancer metastatic potential and epithelial-mesenchymal transition. Pathol –Res Pract. 2020;216(7):153026.

    Article  PubMed  CAS  Google Scholar 

  • Czerwinska P, Jaworska AM, Wlodarczyk NA, Cisek M, Karwacka M, Lipowicz J, et al. The association between bromodomain proteins and cancer stemness in different solid tumor types. Int J Cancer. 2022;150(11):1838–49.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Davalos V, Esteller M. Cancer epigenetics in clinical practice. CA Cancer J Clin. 2022.

  • Dawson MA, Kouzarides T. Cancer epigenetics: from mechanism to therapy. Cell. 2012;150(1):12–27.

    Article  PubMed  CAS  Google Scholar 

  • de Lera AR, Ganesan A. Epigenetic polypharmacology: from combination therapy to multitargeted drugs. Clin Epigen. 2016;8:1–21.

    Google Scholar 

  • De Souza C, Chatterji P, B. HDAC inhibitors as novel anti-cancer therapeutics. Recent Patents Anti-Cancer Drug Discov. 2015;10(2):145–62.

    Article  Google Scholar 

  • Del Gaudio N, Di Costanzo A, Liu NQ, Conte L, Migliaccio A, Vermeulen M, et al. BRD9 binds cell type-specific chromatin regions regulating leukemic cell survival via STAT5 inhibition. Cell Death Dis. 2019;10(5):338.

    Article  PubMed  PubMed Central  Google Scholar 

  • Du W, Gao A, Herman JG, Wang L, Zhang L, Jiao S, Guo M. Methylation of NRN1 is a novel synthetic lethal marker of PI3K-Akt-mTOR and ATR inhibitors in esophageal cancer. Cancer Sci. 2021;112(7):2870–83.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Duan R, Du W, Guo W. EZH2: a novel target for cancer treatment. J Hematol Oncol. 2020;13(1):1–12.

    Article  Google Scholar 

  • Dumitrescu RG. Alcohol-induced epigenetic changes in cancer. Cancer Epigen Precis Med Methods Protoc. 2018;157–72.

  • Ebrahimi N, Parkhideh S, Samizade S, Esfahani AN, Samsami S, Yazdani E, et al. Crosstalk between lncRNAs in the apoptotic pathway and therapeutic targets in cancer. Cyto Growth Fact Rev. 2022.

  • Eden A, Gaudet F, Waghmare A, Jaenisch R. Chromosomal instability and tumors promoted by DNA hypomethylation. Science. 2003;300(5618):455–5.

    Article  PubMed  CAS  Google Scholar 

  • Ehrlich M. DNA methylation in cancer: too much, but also too little. Oncogene. 2002;21(35):5400–13.

    Article  PubMed  CAS  Google Scholar 

  • Ehrlich M. DNA hypomethylation in cancer cells. Epigenomics. 2009;1(2):239–59.

    Article  PubMed  CAS  Google Scholar 

  • Eleutherakis-Papaiakovou E, Kanellias N, Kastritis E, Gavriatopoulou M, Terpos E, Dimopoulos MA. Efficacy of panobinostat for the treatment of multiple myeloma. J Oncol. 2020;2020.

  • Esteller M. Epigenetics in cancer. New Eng J Med. 2008;358(11):1148–59.

    Article  PubMed  CAS  Google Scholar 

  • Fan L, Cao Q, Liu J, Zhang J, Li B. Circular RNA profiling and its potential for esophageal squamous cell cancer diagnosis and prognosis. Mol Cancer. 2019a;18:1–6.

    CAS  Google Scholar 

  • Fan Y, Bian X, Qian P, Wen J, Yan P, Luo Y, et al. miRNA-30a-3p inhibits metastasis and enhances radiosensitivity in esophageal carcinoma by targeting insulin-like growth factor 1 receptor. Mol Med Rep. 2019b;20(1):81–94.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Fang MZ, Wang Y, Ai N, Hou Z, Sun Y, Lu H, et al. Tea polyphenol (−)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines. Cancer Res. 2003;63(22):7563–70.

    PubMed  CAS  Google Scholar 

  • Fang MZ, Chen D, Sun Y, Jin Z, Christman JK, Yang CS. Reversal of hypermethylation and reactivation of p16INK4a, RARβ, and MGMT genes by genistein and other isoflavones from soy. Clin Cancer Res. 2005;11(19):7033–41.

    Article  PubMed  CAS  Google Scholar 

  • Fardi M, Solali S, Hagh MF. Epigenetic mechanisms as a new approach in cancer treatment: an updated review. Genes Dis. 2018;5(4):304–11.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fecteau RE, Kong J, Kresak A, Brock W, Song Y, Fujioka H, et al. Association between germline mutation in VSIG10L and familial Barrett neoplasia. JAMA Oncol. 2016;2(10):1333–9.

    Article  PubMed  PubMed Central  Google Scholar 

  • Feingold PL, Surman DR, Brown K, Xu Y, McDuffie LA, Shukla V, et al. Induction of thioredoxin-interacting protein by a histone deacetylase inhibitor, entinostat, is associated with DNA damage and apoptosis in esophageal adenocarcinoma TXNIP is associated with apoptosis in esophageal cancer. Mol Cancer Therap. 2018;17(9):2013–23.

    Article  CAS  Google Scholar 

  • Ferlay J, Colombet M, Soerjomataram I, Parkin DM, Piñeros M, Znaor A, Bray F. Cancer statistics for the year 2020: an overview. Int J Cancer. 2021;149(4):778–89.

    Article  CAS  Google Scholar 

  • Fraga MF, Ballestar E, Villar-Garea A, Boix-Chornet M, Espada J, Schotta G, et al. Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat Gen. 2005;37(4):391–400.

    Article  CAS  Google Scholar 

  • Gaiti F, Chaligne R, Gu H, Brand RM, Kothen-Hill S, Schulman RC, et al. Epigenetic evolution and lineage histories of chronic lymphocytic leukaemia. Nature. 2019;569(7757):576–80.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gao P, Wang D, Liu M, Chen S, Yang Z, Zhang J, et al. DNA methylation-mediated repression of exosomal miR-652-5p expression promotes oesophageal squamous cell carcinoma aggressiveness by targeting PARG and VEGF pathways. PLoS Gen. 2020;16(4):e1008592.

    Article  CAS  Google Scholar 

  • Gelato KA, Adler D, Ocker M, Haendler B. Targeting epigenetic regulators for cancer therapy: modulation of bromodomain proteins, methyltransferases, demethylases, and microRNAs. Exp Opin Therap Targets. 2016;20(7):783–99.

    Article  CAS  Google Scholar 

  • Gil J, Ramírez-Torres A, Encarnación-Guevara S. Lysine acetylation and cancer: a proteomics perspective. J Proteom. 2017;150:297–309.

    Article  CAS  Google Scholar 

  • Greer EL, Shi Y. Histone methylation: a dynamic mark in health, disease and inheritance. Nat Rev Gen. 2012;13(5):343–57.

    Article  CAS  Google Scholar 

  • Grixti JM, Ayers D. Long noncoding RNAs and their link to cancer. Non-coding RNA Res. 2020;5(2):77–82.

    Article  CAS  Google Scholar 

  • Guo M, Ren J, House MG, Qi Y, Brock MV, Herman JG. Accumulation of promoter methylation suggests epigenetic progression in squamous cell carcinoma of the esophagus. Clin Cancer Res. 2006;12(15):4515–22.

    Article  PubMed  CAS  Google Scholar 

  • Guo W, Zhang M, Shen S, Guo Y, Kuang G, Yang Z, Dong Z. Aberrant methylation and decreased expression of the TGF-β/Smad target gene FBXO32 in esophageal squamous cell carcinoma. Cancer. 2014;120(16):2412–23.

    Article  PubMed  CAS  Google Scholar 

  • Guo YL, Shan BE, Guo W, Dong ZM, Zhou Z, Shen SP, et al. Aberrant methylation of DACT1 and DACT2 are associated with tumor progression and poor prognosis in esophageal squamous cell carcinoma. J Biomed Sci. 2017;24(1):1–12.

    Article  CAS  Google Scholar 

  • Guo M, Peng Y, Gao A, Du C, Herman JG. Epigenetic heterogeneity in cancer. Biomarker Res. 2019;7(1):1–19.

    Article  Google Scholar 

  • Han W, Cui H, Liang J, Su X. Role of MicroRNA-30c in cancer progression. J Cancer. 2020;11(9):2593.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, Kjems J. Natural RNA circles function as efficient microRNA sponges. Nature. 2013;495(7441):384–8.

    Article  PubMed  CAS  Google Scholar 

  • Harada K, Baba Y, Ishimoto T, Kosumi K, Tokunaga R, Izumi D, et al. Suppressor microRNA-145 is epigenetically regulated by promoter hypermethylation in esophageal squamous cell carcinoma. Antican Res. 2015;35(9):4617–24.

    CAS  Google Scholar 

  • He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Gen. 2004;5(7):522–31.

    Article  CAS  Google Scholar 

  • He Y, Wang Y, Li P, Zhu S, Wang J, Zhang S. Identification of GPX3 epigenetically silenced by CpG methylation in human esophageal squamous cell carcinoma. Digest Dis Sci. 2011;56:681–8.

    Article  PubMed  CAS  Google Scholar 

  • He W, Gong S, Wang X, Dong X, Cheng H. DNA methylation integratedly modulates the expression of Pit-Oct-Unt transcription factors in esophageal squamous cell carcinoma. J Cancer. 2021;12(6):1634.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • He W, Lin S, Guo Y, Wu Y, Zhang LL, Deng Q, et al. Targeted demethylation at ZNF154 promotor upregulates ZNF154 expression and inhibits the proliferation and migration of esophageal squamous carcinoma cells. Oncogene. 2022;41(40):4537–46.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hong DS, Kang YK, Borad M, Sachdev J, Ejadi S, Lim HY, et al. Phase 1 study of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumours. Bri J Cancer. 2020;122(11):1630–7.

    Article  CAS  Google Scholar 

  • Hoshimoto S, Takeuchi H, Ono S, Sim MS, Huynh JL, Huang SK, et al. Genome–wide hypomethylation and specific tumor-related gene hypermethylation are associated with esophageal squamous cell carcinoma outcome. J Thor Oncol. 2015;10(3):509–17.

    Article  CAS  Google Scholar 

  • Hu X, Wu D, He X, Zhao H, He Z, Lin J, et al. circGSK3β promotes metastasis in esophageal squamous cell carcinoma by augmenting β-catenin signaling. Mol Cancer. 2019;18:1–14.

    Article  PubMed  PubMed Central  Google Scholar 

  • Huang M, Zhang J, Yan C, Li X, Zhang J, Ling R. Small molecule HDAC inhibitors: Promising agents for breast cancer treatment. Bioorg Chem. 2019;91:103184.

    Article  PubMed  CAS  Google Scholar 

  • Huang WJ, Wang Y, Liu S, Yang J, Guo SX, Wang L, ... Fan YF. RETRACTED: silencing circular RNA hsa_circ_0000977 suppresses pancreatic ductal adenocarcinoma progression by stimulating miR-874-3p and inhibiting PLK1 expression. 2018b.

  • Huang X, Zhou X, Hu Q, Sun B, Deng M, Qi X, Lü M. Advances in esophageal cancer: a new perspective on pathogenesis associated with long non-coding RNAs. Cancer Lett. 2018b;413:94–101.

    Article  PubMed  CAS  Google Scholar 

  • Iwagami S, Baba Y, Watanabe M, Shigaki H, Miyake K, Ishimoto T, et al. LINE-1 hypomethylation is associated with a poor prognosis among patients with curatively resected esophageal squamous cell carcinoma. Ann Surg. 2013;257(3):449–55.

    Article  PubMed  Google Scholar 

  • Jeck WR, Sorrentino JA, Wang K, Slevin MK, Burd CE, Liu J, et al. Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA. 2013;19(2):141–57.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA: a Cancer J Clin. 2011;61(2):69–90.

    Google Scholar 

  • Jenuwein T, Allis CD. Translating the histone code. Science. 2001;293(5532):1074–80.

    Article  PubMed  CAS  Google Scholar 

  • Jian Z, Han Y, Zhang W, Li C, Guo W, Feng X, et al. Anti-tumor effects of dual PI3K-HDAC inhibitor CUDC-907 on activation of ROS-IRE1α-JNK-mediated cytotoxic autophagy in esophageal cancer. Cell Biosci. 2022;12(1):1–18.

    Article  Google Scholar 

  • Jiang W, Wen D, Lulu Gong Y, Wang ZL, Yin F. Circular RNA hsa_circ_0000673 promotes hepatocellular carcinoma malignance by decreasing miR-767-3p targeting SET. Biochem Biophys Res Commun. 2018;500(2):211–6.

    Article  PubMed  CAS  Google Scholar 

  • Jin YQ, Miao DL. Multiomic analysis of methylation and transcriptome reveals a novel signature in esophageal cancer. Dose-Res. 2020;18(3):1559325820942075.

    Article  CAS  Google Scholar 

  • Jin Y, Huo B, Fu X, Hao T, Zhang Y, Guo Y, Hu X. LSD1 collaborates with EZH2 to regulate expression of interferon-stimulated genes. Biomed Pharm. 2017;88:728–37.

    Article  CAS  Google Scholar 

  • John RM, Rougeulle C. Developmental epigenetics: phenotype and the flexible epigenome. Front Cell Dev Biol. 2018;6:130.

    Article  PubMed  PubMed Central  Google Scholar 

  • Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nat Rev Gene. 2002;3(6):415–28.

    Article  CAS  Google Scholar 

  • Jones PA, Ohtani H, Chakravarthy A, De Carvalho DD. Epigenetic therapy in immune-oncology. Nat Rev Cancer. 2019;19(3):151–61.

    Article  PubMed  CAS  Google Scholar 

  • Juergens RA, Wrangle J, Vendetti FP, Murphy SC, Zhao M, Coleman B, et al. Combination epigenetic therapy has efficacy in patients with refractory advanced non–small cell lung cancer combinatorial epigenetic therapy for lung cancer. Cancer Discov. 2011;1(7):598–607.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kadoch C, Hargreaves DC, Hodges C, Elias L, Ho L, Ranish J, Crabtree GR. Proteomic and bioinformatic analysis of mammalian SWI/SNF complexes identifies extensive roles in human malignancy. Nat Gene. 2013;45(6):592–601.

    Article  CAS  Google Scholar 

  • Kahng DH, Kim GH, Park SJ, Kim S, Lee MW, Lee BE, Hoseok I. MicroRNA expression in plasma of esophageal squamous cell carcinoma patients. J Kor Med Sci. 2022;37(24).

  • Kanwal R, Gupta S. Epigenetic modifications in cancer. Clin Gen. 2012;81(4):303–11.

    Article  CAS  Google Scholar 

  • Karim RM, Schönbrunn E. An advanced tool to interrogate BRD9. J Med Chem. 2016;59(10):4459–61.

    Article  PubMed  CAS  Google Scholar 

  • Karim RM, Chan A, Zhu JY, Schönbrunn E. Structural basis of inhibitor selectivity in the BRD7/9 subfamily of bromodomains. J Med Chem. 2020;63(6):3227–37.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kawakami K, Brabender J, Lord RV, Groshen S, Greenwald BD, Krasna MJ, et al. Hypermethylated APC DNA in plasma and prognosis of patients with esophageal adenocarcinoma. J Nat Cancer Inst. 2000;92(22):1805–11.

    Article  PubMed  CAS  Google Scholar 

  • Kaya Z, Almalı N, Sahin ES, Duran S, Görgisen G, Ates C. Association of insulin-like growth factor binding protein-7 promoter methylation with esophageal cancer in peripheral blood. Mol Biol Rep. 2022;49(5):3423–31.

    Article  PubMed  CAS  Google Scholar 

  • Kaz AM, Grady WM. Epigenetic biomarkers in esophageal cancer. Cancer Lett. 2014;342(2):193–9.

    Article  PubMed  CAS  Google Scholar 

  • Ke Q, Li Q, Ellen TP, Sun H, Costa M. Nickel compounds induce phosphorylation of histone H3 at serine 10 by activating JNK–MAPK pathway. Carcinogenesis. 2008;29(6):1276–81.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Khalid R, Naveed H, Khalid Z. Computational prediction of disease related lncRNAs using machine learning. Sci Rep. 2023;13(1):806.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Khalil AM, Guttman M, Huarte M, Garber M, Raj A, Rivea Morales D, et al. Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Nat Acad Sci. 2009;106(28):11667–72.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kou Y, Koag MC, Lee S. Promutagenicity of 8-chloroguanine, a major inflammation-induced halogenated DNA lesion. Molecules. 2019;24(19):3507.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kouzarides T. Chromatin modifications and their function. Cell. 2007;128(4):693–705.

    Article  PubMed  CAS  Google Scholar 

  • Krämer KF, Moreno N, Frühwald MC, Kerl K. BRD9 inhibition, alone or in combination with cytostatic compounds as a therapeutic approach in rhabdoid tumors. Int J Mol Sci. 2017;18(7):1537.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lai AC, Crews CM. Induced protein degradation: an emerging drug discovery paradigm. Nat Rev Drug Discov. 2017;16(2):101–14.

    Article  PubMed  CAS  Google Scholar 

  • Lawrence MS, Stojanov P, Mermel CH, Robinson JT, Garraway LA, Golub TR, et al. Discovery and saturation analysis of cancer genes across 21 tumour types. Nature. 2014;505(7484):495–501.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lee BH, Yegnasubramanian S, Lin X, Nelson WG. Procainamide is a specific inhibitor of DNA methyltransferase 1. J Biol Chem. 2005;280(49):40749–56.

    Article  PubMed  CAS  Google Scholar 

  • Lee EJ, Lee BB, Han J, Cho EY, Shim YM, Park J, Kim DH. CpG island hypermethylation of E-cadherin (CDH1) and integrin α4 is associated with recurrence of early stage esophageal squamous cell carcinoma. Int J Cancer. 2008;123(9):2073–9.

    Article  PubMed  CAS  Google Scholar 

  • Li B, Wang B, Niu LJ, Jiang L, Qiu CC. Hypermethylation of multiple tumor-related genes associated with DMNT3b up-regulation served as a biomarker for early diagnosis of esophageal squamous cell carcinoma. Epigenetics. 2011a;6(3):307–16.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Li X, Lin R, Li J. Epigenetic silencing of microRNA-375 regulates PDK1 expression in esophageal cancer. Digest Dis Sci. 2011b;56:2849–56.

    Article  PubMed  CAS  Google Scholar 

  • Li J, Sun D, Pu W, Wang J, Peng Y. Circular RNAs in cancer: biogenesis, function, and clinical significance. Trends Cancer. 2020a;6(4):319–36.

    Article  PubMed  CAS  Google Scholar 

  • Li L, Gao L, Zhou H, Shi C, Zhang X, Zhang D, Liu H. High expression level of BRD4 is associated with a poor prognosis and immune infiltration in esophageal squamous cell carcinoma. Digest Dis Sci. 2023:1–12.

  • Li M, Cui L, Zhang J, Wang S, Du M. The critical roles of circular RNAs in basic research and clinical application of female reproductive–related diseases. Reprod Sci. 2022a:1–14.

  • Li SM, He LR, Chen JW, Zhou J, Nie RC, Jin XH, et al. JMJD3 promotes esophageal squamous cell carcinoma pathogenesis through epigenetic regulation of MYC. Signal Trans Target Ther. 2020b;5(1):165.

    Article  CAS  Google Scholar 

  • Li N, Zhao Z, Miao F, Cai S, Liu P, Yu Y, Wang B. Silencing of long non-coding RNA LINC01270 inhibits esophageal cancer progression and enhances chemosensitivity to 5-fluorouracil by mediating GSTP1methylation. Cancer Gene Ther. 2021a;28(5):471–85.

    Article  PubMed  CAS  Google Scholar 

  • Li Z, Li S, Wen Y, Chen J, Liu K, Jia J. MiR-495 inhibits cisplatin resistance and angiogenesis in esophageal cancer by targeting ATP7A. Technol Cancer Res Treat. 2021b;20:15330338211039127.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Li P, Liu X, Xing W, Qiu H, Li R, Liu S, Sun H. Exosome-derived miR-200a promotes esophageal cancer cell proliferation and migration via the mediating Keap1 expression. Mol Cell Biochem. 2022b;477(4):1295–308.

    Article  PubMed  CAS  Google Scholar 

  • Liang Z, Huang J, Sun G. Tip60-siRNA regulates ABCE1 acetylation and inhibits the proliferation, migration and invasion of esophageal cancer via the Wnt pathway. J Biosci Med. 2022;10(10):210–20.

    CAS  Google Scholar 

  • Liao L, Yao ZT, Fang WK, He QY, Xu WW, Li B. Epigenetics in esophageal cancer: from mechanisms to therapeutics. Small Methods. 2020;4(10):2000391.

    Article  Google Scholar 

  • Lin C, Xi Y, Yu H, Wang Z, Chen X, Shen W. circRNA TCFL5 promote esophageal cancer progression by modulating M2 macrophage polarization via the miR-543-FMNL2 axis. J Oncol. 2022.

  • Lin DC, Wang MR, Koeffler HP. Genomic and epigenomic aberrations in esophageal squamous cell carcinoma and implications for patients. Gastroenterology. 2018a;154(2):374–89.

    Article  PubMed  Google Scholar 

  • Lin Q, Ling YB, Chen JW, Zhou CR, Chen J, Li X, Huang MS. Circular RNA circCDK13 suppresses cell proliferation, migration and invasion by modulating the JAK/STAT and PI3K/AKT pathways in liver cancer. Int J Oncol. 2018b;53(1):246–56.

    PubMed  CAS  Google Scholar 

  • Lin S, Zhou M, Li Y, Chen Y, Xu W, Xia W, et al. H3K27 trimethylation and H3K9 dimethylation as poor prognostic markers for patients with esophageal squamous cell carcinoma. Int J Clin Exp Pathol. 2019a;12(7):2657.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Lin Z, Li D, Cheng W, Wu J, Wang K, Hu Y. MicroRNA-181 functions as an antioncogene and mediates NF-gκB pathway by targeting RTKN2 in ovarian cancers. Reprod Sci. 2019b;26(8):1071–81.

    Article  PubMed  Google Scholar 

  • Lin L, Cheng X, Yin D. Aberrant DNA methylation in esophageal squamous cell carcinoma: biological and clinical implications. Front Oncol. 2020;10:549850.

    Article  PubMed  PubMed Central  Google Scholar 

  • Litzenburger UM, Buenrostro JD, Wu B, Shen Y, Sheffield NC, Kathiria A, et al. Single-cell epigenomic variability reveals functional cancer heterogeneity. Gen Biol. 2017;18(1):1–12.

    Article  Google Scholar 

  • Liu S, Tan J. DNA methyltransferase inhibitors (DNMTis) as sensitizing agents to overcome chemoresistance. In: Epigenetic Regulation in Overcoming Chemoresistance. Academic Press; 2021. p. 9–23.

    Chapter  Google Scholar 

  • Liu HC, Zhang GH, Liu YH, Wang P, Ma JF, Su LS, et al. TPX2 siRNA regulates growth and invasion of esophageal cancer cells. Biomed Pharma. 2014;68(7):833–9.

    Article  CAS  Google Scholar 

  • Liu R, Gu J, Jiang P, Zheng Y, Liu X, Jiang X, et al. DNMT1–microRNA126 epigenetic circuit contributes to esophageal squamous cell carcinoma growth via ADAM9–EGFR–AKT signaling DNMT1–microRNA126 epigenetic circuit regulates ESCC growth. Clin Cancer Res. 2015;21(4):854–63.

    Article  PubMed  CAS  Google Scholar 

  • Liu NA, Zhao R, Ma Y, Wang D, Yan C, Zhou D, et al. The development of epigenetics and related inhibitors for targeted drug design in cancer therapy. Curr Topics Med Chem. 2018;18(28):2380–94.

    Article  CAS  Google Scholar 

  • Liu J, Xue N, Guo Y, Niu K, Gao L, Zhang S, et al. CircRNA_100367 regulated the radiation sensitivity of esophageal squamous cell carcinomas through miR-217/Wnt3 pathway. Aging (Albany NY). 2019;11(24):12412.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liu D, Wu K, Yang Y, Zhu D, Zhang C, Zhao S. Long noncoding RNA ADAMTS9-AS2 suppresses the progression of esophageal cancer by mediating CDH3 promoter methylation. Mol Carcinogen. 2020a;59(1):32–44.

    Article  CAS  Google Scholar 

  • Liu H, Zhang Q, Lou Q, Zhang X, Cui Y, Wang P, et al. Differential analysis of lncRNA, miRNA and mRNA expression profiles and the prognostic value of lncRNA in esophageal cancer. Pathol Oncol Res. 2020b;26:1029–39.

    Article  PubMed  CAS  Google Scholar 

  • Liu Y, Zhang M, He T, Yang W, Wang L, Zhang L, Guo M. Epigenetic silencing of IGFBPL1 promotes esophageal cancer growth by activating PI3K-AKT signaling. Clin Epigen. 2020c;12:1–12.

    Article  Google Scholar 

  • Liu D, Liu Y, Qi B, Gu C, Huo S, Zhao B. Trichostatin A promotes esophageal squamous cell carcinoma cell migration and EMT through BRD4/ERK1/2-dependent pathway. Cancer Med. 2021a;10(15):5235–45.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liu Z, Gu S, Wu K, Li L, Dong C, Wang W, Zhou Y. CircRNA-DOPEY2 enhances the chemosensitivity of esophageal cancer cells by inhibiting CPEB4-mediated Mcl-1 translation. J Exp Clin Cancer Res. 2021b;40:1–17.

    Article  CAS  Google Scholar 

  • Long HK, King HW, Patient RK, Odom DT, Klose RJ. Protection of CpG islands from DNA methylation is DNA-encoded and evolutionarily conserved. Nucl Acids Res. 2016;44(14):6693–706.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lopez-Serra P, Esteller M. DNA methylation-associated silencing of tumor-suppressor microRNAs in cancer. Oncogene. 2012;31(13):1609–22.

    Article  PubMed  CAS  Google Scholar 

  • Lu Z, Yun Y, Zhang Y, Ou Y, Wang M. Promotion of microRNA-146a by histone deacetylase 4 silencing contributes to radiosensitization of esophageal carcinoma. J Trans Med. 2022;20(1):1–13.

    Article  CAS  Google Scholar 

  • Luo YH, Zhu XZ, Huang KW, Zhang Q, Fan YX, Yan PW, Wen J. Emerging roles of circular RNA hsa_circ_0000064 in the proliferation and metastasis of lung cancer. Biomed Pharm. 2017;96:892–8.

    Article  CAS  Google Scholar 

  • Luo G, Li R, Li Z. CircRNA circFNDC3B promotes esophageal cancer progression via cell proliferation, apoptosis, and migration regulation. Int J Clin Exp Pathol. 2018a;11(8):4188.

    PubMed  PubMed Central  Google Scholar 

  • Luo M, Li Y, Shi X, Yang W, Zhou F, Sun N, He J. Aberrant methylation of EYA4 promotes epithelial-mesenchymal transition in esophageal squamous cell carcinoma. Cancer Sci. 2018b;109(6):1811–24.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Luo XJ, He MM, Liu J, Zheng JB, Wu QN, Chen YX, et al. LncRNA TMPO-AS1 promotes esophageal squamous cell carcinoma progression by forming biomolecular condensates with FUS and p300 to regulate TMPO transcription. Exp Mol Med. 2022;54(6):834–47.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ma K, Cao B, Guo M. The detective, prognostic, and predictive value of DNA methylation in human esophageal squamous cell carcinoma. Clin Epigen. 2016;8:1–9.

    Article  Google Scholar 

  • Ma S, Liu T, Xu L, Wang Y, Zhou J, Huang T, et al. Histone deacetylases inhibitor MS-275 suppresses human esophageal squamous cell carcinoma cell growth and progression via the PI3K/Akt/mTOR pathway. J Cell Physiol. 2019;234(12):22400–10.

    Article  PubMed  CAS  Google Scholar 

  • Ma Y, He S, Gao A, Zhang Y, Zhu Q, Wang P, et al. Methylation silencing of TGF-β receptor type II is involved in malignant transformation of esophageal squamous cell carcinoma. Clin Epigen. 2020;12(1):1–12.

    Article  Google Scholar 

  • Macedo-Silva C, Miranda-Gonçalves V, Lameirinhas A, Lencart J, Pereira A, Lobo J, et al. JmjC-KDMs KDM3A and KDM6B modulate radioresistance under hypoxic conditions in esophageal squamous cell carcinoma. Cell Death Dis. 2020;11(12):1068.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Martin LJ, Koegl M, Bader G, Cockcroft XL, Fedorov O, Fiegen D, et al. Structure-based design of an in vivo active selective BRD9 inhibitor. J Med Chem. 2016;59(10):4462–75.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Matsushima K, Isomoto H, Inoue N, Nakayama T, Hayashi T, Nakayama M, et al. MicroRNA signatures in Helicobacter pylori-infected gastric mucosa. Int J Cancer. 2011;128(2):361–70.

    Article  PubMed  CAS  Google Scholar 

  • Mazur PK, Herner A, Mello SS, Wirth M, Hausmann S, Sánchez-Rivera FJ, et al. Combined inhibition of BET family proteins and histone deacetylases as a potential epigenetics-based therapy for pancreatic ductal adenocarcinoma. Nat Med. 2015;21(10):1163–71.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature. 2013;495(7441):333–8.

    Article  PubMed  CAS  Google Scholar 

  • Michel BC, D’Avino AR, Cassel SH, Mashtalir N, McKenzie ZM, McBride MJ, et al. A non-canonical SWI/SNF complex is a synthetic lethal target in cancers driven by BAF complex perturbation. Nat Cell Biol. 2018;20(12):1410–20.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mondal P, Natesh J, Penta D, Meeran SM. Progress and promises of epigenetic drugs and epigenetic diets in cancer prevention and therapy: a clinical update. In: Seminars in Cancer Biology, vol. 83. Academic Press; 2022. p. 503–22.

    Google Scholar 

  • Moore LD, Le T, Fan G. DNA methylation and its basic function. Neuropsychopharmacology. 2013;38(1):23–38.

    Article  PubMed  CAS  Google Scholar 

  • Muwonge R, Ramadas K, Sankila R, Thara S, Thomas G, Vinoda J, Sankaranarayanan R. Role of tobacco smoking, chewing and alcohol drinking in the risk of oral cancer in Trivandrum, India: a nested case-control design using incident cancer cases. Oral Oncol. 2008;44(5):446–54.

    Article  PubMed  CAS  Google Scholar 

  • Nagaraju GP, Kasa P, Dariya B, Surepalli N, Peela S, Ahmad S. Epigenetics and therapeutic targets in gastrointestinal malignancies. Drug Discov Today. 2021;26(10):2303–14.

    Article  PubMed  CAS  Google Scholar 

  • Nam AS, Chaligne R, Landau DA. Integrating genetic and non-genetic determinants of cancer evolution by single-cell multi-omics. Nat Rev Gen. 2021;22(1):3–18.

    Article  CAS  Google Scholar 

  • Napier KJ, Scheerer M, Misra S. Esophageal cancer: a review of epidemiology, pathogenesis, staging workup and treatment modalities. W J Gastrointest Oncol. 2014;6(5):112.

    Article  Google Scholar 

  • Narayan A, Ji W, Zhang XY, Marrogi A, Graff JR, Baylin SB, Ehrlich M. Hypomethylation of pericentromeric DNA in breast adenocarcinomas. Int J Cancer. 1998;77(6):833–8.

    Article  PubMed  CAS  Google Scholar 

  • Nepali K, Liou JP. Recent developments in epigenetic cancer therapeutics: Clinical advancement and emerging trends. J Biomed Sci. 2021;28(1):1–58.

    Article  Google Scholar 

  • Niu H, Song F, Wei H, Li Y, Huang H, Wu C. Inhibition of BRD4 suppresses the growth of esophageal squamous cell carcinoma. Cancer Invest. 2021;39(10):826–41.

    Article  PubMed  CAS  Google Scholar 

  • Nyhan MJ, O’Donovan TR, Boersma AW, Wiemer EA, McKenna SL. MiR-193b promotes autophagy and non-apoptotic cell death in oesophageal cancer cells. BMC Cancer. 2016;16:1–13.

    Article  Google Scholar 

  • O'Rourke CJ, Munoz-Garrido P, Aguayo EL, Andersen JB. Epigenome dysregulation in cholangiocarcinoma. Biochim et Biophys Acta (BBA)-Mol Basis Dis. 2018;1864(4):1423–34.

    Article  CAS  Google Scholar 

  • Pan Z, Lin J, Wu D, He X, Wang W, Hu X, et al. Hsa_circ_0006948 enhances cancer progression and epithelial-mesenchymal transition through the miR-490-3p/HMGA2 axis in esophageal squamous cell carcinoma. Aging (Albany NY). 2019;11(24):11937.

    Article  PubMed  PubMed Central  Google Scholar 

  • Pan C, Chen G, Zhao X, Xu X, Liu J. lncRNA BBOX1-AS1 silencing inhibits esophageal squamous cell cancer progression by promoting ferroptosis via miR-513a-3p/SLC7A11 axis. Eur J Pharm. 2022;934:175317.

    Article  CAS  Google Scholar 

  • Pandya G, Kirtonia A, Sethi G, Pandey AK, Garg M. The implication of long non-coding RNAs in the diagnosis, pathogenesis and drug resistance of pancreatic ductal adenocarcinoma and their possible therapeutic potential. Biochim et Biophys Acta (BBA)-Rev Cancer. 2020;1874(2):188423.

    Article  CAS  Google Scholar 

  • Pang Y, Liu J, Li X, Zhang Y, Zhang B, Zhang J, et al. Nano Let-7b sensitization of eliminating esophageal cancer stem-like cells is dependent on blockade of Wnt activation of symmetric division. Int J Oncol. 2017;51(4):1077–88.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pauli A, Rinn JL, Schier AF. Non-coding RNAs as regulators of embryogenesis. Nat Rev Gen. 2011;12(2):136–49.

    Article  CAS  Google Scholar 

  • Pechalrieu D, Etievant C, Arimondo PB. DNA methyltransferase inhibitors in cancer: from pharmacology to translational studies. Biochem Pharm. 2017;129:1–13.

    Article  PubMed  CAS  Google Scholar 

  • Pérez-Salvia M, Esteller M. Bromodomain inhibitors and cancer therapy: from structures to applications. Epigenetics. 2017;12(5):323–39.

    Article  PubMed  Google Scholar 

  • Pina IC, Gautschi JT, Wang GYS, Sanders ML, Schmitz FJ, France D, et al. Psammaplins from the sponge pseudoceratina p urpurea: inhibition of both histone deacetylase and DNA methyltransferase. J Org Chem. 2003;68(10):3866–73.

    Article  PubMed  CAS  Google Scholar 

  • Qin T, Liu W, Huo J, Li L, Zhang X, Shi X, et al. SIRT1 expression regulates the transformation of resistant esophageal cancer cells via the epithelial-mesenchymal transition. Biomed Pharm. 2018;103:308–16.

    Article  CAS  Google Scholar 

  • Qiu BQ, Lin XH, Ye XD, Huang W, Pei X, Xiong D, et al. Long non-coding RNA PSMA3-AS1 promotes malignant phenotypes of esophageal cancer by modulating the miR-101/EZH2 axis as a ceRNA. Aging (Albany NY). 2020;12(2):1843.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Remillard D, Buckley DL, Paulk J, Brien GL, Sonnett M, Seo HS, et al. Degradation of the BAF complex factor BRD9 by heterobifunctional ligands. Angewandte Chem Int Ed. 2017;56(21):5738–43.

    Article  CAS  Google Scholar 

  • Robertson KD. DNA methylation and human disease. Nat Rev Gen. 2005;6(8):597–610.

    Article  CAS  Google Scholar 

  • Salim U, Kumar A, Kulshreshtha R, Vivekanandan P. Biogenesis, characterization, and functions of mirtrons. Wiley Interdis Rev: RNA. 2022;13(1):e1680.

    Article  CAS  Google Scholar 

  • Sand M, Bechara FG, Gambichler T, Sand D, Bromba M, Hahn SA, et al. Circular RNA expression in cutaneous squamous cell carcinoma. J Dermatol Sci. 2016;83(3):210–8.

    Article  PubMed  CAS  Google Scholar 

  • Sato S, Dacher M, Kurumizaka H. Nucleosome structures built from highly divergent histones: parasites and giant DNA viruses. Epigenomes. 2022;6(3):22.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Satpathy AT, Granja JM, Yost KE, Qi Y, Meschi F, McDermott GP, et al. Massively parallel single-cell chromatin landscapes of human immune cell development and intratumoral T cell exhaustion. Nat Biotechnol. 2019;37(8):925–36.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Schallenberg S, Bork J, Essakly A, Alakus H, Buettner R, Hillmer AM, et al. Loss of the SWI/SNF-ATPase subunit members SMARCF1 (ARID1A), SMARCA2 (BRM), SMARCA4 (BRG1) and SMARCB1 (INI1) in oesophageal adenocarcinoma. BMC Cancer. 2020;20(1):1–12.

    Article  Google Scholar 

  • Schizas D, Mastoraki A, Naar L, Spartalis E, Tsilimigras DI, Karachaliou GS, et al. Concept of histone deacetylases in cancer: reflections on esophageal carcinogenesis and treatment. W J Gastroenterol. 2018;24(41):4635.

    Article  CAS  Google Scholar 

  • Schneider BJ, Shah MA, Klute K, Ocean A, Popa E, Altorki N, et al. Phase I study of epigenetic priming with azacitidine prior to standard neoadjuvant chemotherapy for patients with resectable gastric and esophageal adenocarcinoma: evidence of tumor hypomethylation as an indicator of major histopathologic response neoadjuvant epigenetic priming for upper gastrointestinal adenocarcinoma. Clin Cancer Res. 2017;23(11):2673–80.

    Article  PubMed  CAS  Google Scholar 

  • Seto E, Yoshida M. Erasers of histone acetylation: the histone deacetylase enzymes. Cold Spring Harb Persp Biol. 2014;6(4):a018713.

    Article  Google Scholar 

  • Shen S, Liang J, Liang X, Wang G, Feng B, Guo W, et al. SNHG17, as an EMT-related lncRNA, promotes the expression of c-Myc by binding to c-Jun in esophageal squamous cell carcinoma. Cancer Sci. 2022;113(1):319–33.

    Article  PubMed  CAS  Google Scholar 

  • Shi Y, Fang N, Li Y, Guo Z, Jiang W, He Y, et al. Circular RNA LPAR3 sponges microRNA-198 to facilitate esophageal cancer migration, invasion, and metastasis. Cancer Sci. 2020;111(8):2824–36.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Shi Y, Xiang Z, Yang H, Khan S, Li R, Zhou S, et al. Pharmacological targeting of TNS3 with histone deacetylase inhibitor as a therapeutic strategy in esophageal squamous cell carcinoma. Aging (Albany NY). 2021;13(11):15336.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Shi X, Liu X, Huang S, Hao Y, Pan S, Ke Y, et al. miR-4443 promotes radiation resistance of esophageal squamous cell carcinoma via targeting PTPRJ. J Trans Med. 2022;20(1):1–14.

    Article  Google Scholar 

  • Shoda K, Kuwano Y, Ichikawa D, Masuda K. circRNA: a new biomarker and therapeutic target for esophageal cancer. Biomed. 2022;10(7):1643.

    CAS  Google Scholar 

  • Song S, Li Y, Xu Y, Ma L, Pool Pizzi M, Jin J, et al. Targeting Hippo coactivator YAP1 through BET bromodomain inhibition in esophageal adenocarcinoma. Mol Oncol. 2020;14(6):1410–26.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Source: Globocan 2020- Global Cancer Observatory. https://gco.iarc.fr/today/data/factsheets/populations/356-india-fact-sheets.pdf. Accessed 20 Feb 2023.

  • Statello L, Guo C-J, Chen L-L, Huarte M. Gene regulation by long non-coding RNAs and its biological functions. Nat Rev Mol Cell Biol. 2021;22(2):96–118.

    Article  PubMed  CAS  Google Scholar 

  • Strahl BD, Allis CD. The language of covalent histone modifications. Nature. 2000;403(6765):41–5.

    Article  PubMed  CAS  Google Scholar 

  • Straining R, Eighmy W. Tazemetostat: EZH2 inhibitor. J Adv Pract Oncol. 2022;13(2):158.

    Article  PubMed  PubMed Central  Google Scholar 

  • Stresemann C, Brueckner B, Musch T, Stopper H, Lyko F. Functional diversity of DNA methyltransferase inhibitors in human cancer cell lines. Cancer Res. 2006;66(5):2794–800.

    Article  PubMed  CAS  Google Scholar 

  • Su M, Xiao Y, Ma J, Cao D, Zhou Y, Wang H, et al. Long non-coding RNAs in esophageal cancer: molecular mechanisms, functions, and potential applications. J Hematol Oncol. 2018;11(1):1–14.

    Article  Google Scholar 

  • Su H, Wu Y, Fang Y, Shen L, Fei Z, Xie C, Chen M. MicroRNA-301a targets WNT1 to suppress cell proliferation and migration and enhance radiosensitivity in esophageal cancer cells. Oncol Rep. 2019a;41(1):599–607.

    PubMed  CAS  Google Scholar 

  • Su J, Liu X, Zhang S, Yan F, Zhang Q, Chen J. Insight into selective mechanism of class of I-BRD9 inhibitors toward BRD9 based on molecular dynamics simulations. Chem Biol Drug Des. 2019b;93(2):163–76.

    Article  PubMed  CAS  Google Scholar 

  • Subramaniam D, Thombre R, Dhar A, Anant S. DNA methyltransferases: a novel target for prevention and therapy. Front Oncol. 2014;4:80.

    Article  PubMed  PubMed Central  Google Scholar 

  • Sun Q, Hao Q, Prasanth KV. Nuclear long noncoding RNAs: key regulators of gene expression. Trends Gen. 2018;34(2):142–57.

    Article  CAS  Google Scholar 

  • Sun R, Xiang T, Tang J, Peng W, Luo J, Li L, et al. 19q13 KRAB zinc-finger protein ZNF471 activates MAPK10/JNK3 signaling but is frequently silenced by promoter CpG methylation in esophageal cancer. Theranostics. 2020;10(5):2243.

    Article  PubMed  PubMed Central  Google Scholar 

  • Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a Cancer J Clin. 2021;71(3):209–49.

    Google Scholar 

  • Suraweera A, O’Byrne KJ, Richard DJ. Combination therapy with histone deacetylase inhibitors (HDACi) for the treatment of cancer: achieving the full therapeutic potential of HDACi. Front Oncol. 2018;8:92.

    Article  PubMed  PubMed Central  Google Scholar 

  • Suyal G, Pandey P, Saraya A, Sharma R. Tumour suppressor role of microRNA-335-5p in esophageal squamous cell carcinoma by targeting TTK (Mps1). Exp Mol Pathol. 2022;124:104738.

    Article  PubMed  CAS  Google Scholar 

  • Suzuki MM, Bird A. DNA methylation landscapes: provocative insights from epigenomics. Nat Rev Gen. 2008;9(6):465–76.

    Article  CAS  Google Scholar 

  • Taby R, Issa JPJ. Cancer epigenetics. CA: a Cancer J Clin. 2010;60(6):376–92.

    Google Scholar 

  • Tang L, Liou YL, Wan ZR, Tang J, Zhou Y, Zhuang W, Wang G. Aberrant DNA methylation of PAX1, SOX1 and ZNF582 genes as potential biomarkers for esophageal squamous cell carcinoma. Biomed Pharm. 2019;120:109488.

    Article  CAS  Google Scholar 

  • Then EO, Lopez M, Saleem S, Gayam V, Sunkara T, Culliford A, Gaduputi V. Esophageal cancer: an updated surveillance epidemiology and end results database analysis. W J Oncol. 2020;11(2):55.

    Article  Google Scholar 

  • Thrift AP. Global burden and epidemiology of Barrett oesophagus and oesophageal cancer. Nat Rev Gastroenterol Hepatol. 2021;18(6):432–43.

    Article  PubMed  Google Scholar 

  • Toden S, Zumwalt TJ, Goel A. Non-coding RNAs and potential therapeutic targeting in cancer. Biochim et Biophys Acta (BBA)-Rev Cancer. 2021;1875(1):188491.

    Article  CAS  Google Scholar 

  • Turtoi A, Peixoto P, Castronovo V, Bellahcène A. Histone deacetylases and cancer-associated angiogenesis: current understanding of the biology and clinical perspectives. Cri Rev™ Oncogen. 2015;20(1–2).

  • van Nistelrooij AM, Dinjens WN, Wagner A, Spaander MC, van Lanschot JJB, Wijnhoven BP. Hereditary factors in esophageal adenocarcinoma. Gastrointest Tumors. 2014;1(2):93–8.

    Article  PubMed  PubMed Central  Google Scholar 

  • Varambally S, Dhanasekaran SM, Zhou M, Barrette TR, Kumar-Sinha C, Sanda MG, et al. The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature. 2002;419(6907):624–9.

    Article  PubMed  CAS  Google Scholar 

  • Wang Z, Zhu S, Shen M, Liu J, Wang M, Li C, et al. STAT3 is involved in esophageal carcinogenesis through regulation of Oct-1. Carcinogenesis. 2013;34(3):678–88.

    Article  PubMed  CAS  Google Scholar 

  • Wang L, Wu X, Huang P, Lv Z, Qi Y, Wei X, et al. JQ1, a small molecule inhibitor of BRD4, suppresses cell growth and invasion in oral squamous cell carcinoma. Oncol Rep. 2016;36(4):1989–96.

    Article  PubMed  Google Scholar 

  • Wang B, Zhao B, Pang LP, Zhao YD, Guo Q, Wang JW, et al. LPE-1, an orally active pyrimidine derivative, inhibits growth and mobility of human esophageal cancers by targeting LSD1. Pharmacol Res. 2017a;122:66–77.

    Article  PubMed  CAS  Google Scholar 

  • Wang C, Li Z, Shao F, Yang X, Feng X, Shi S, et al. High expression of Collagen Triple Helix Repeat Containing 1 (CTHRC1) facilitates progression of oesophageal squamous cell carcinoma through MAPK/MEK/ERK/FRA-1 activation. J Exp Clin Cancer Res. 2017b;36:1–14.

    Article  CAS  Google Scholar 

  • Wang LX, Shi YL, Zhang LJ, Wang KR, Xiang LP, Cai ZY, et al. Inhibitory effects of (−)-epigallocatechin-3-gallate on esophageal cancer. Molecules. 2019a;24(5):954.

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang L, Wang L, Chang W, Li Y, Wang L. MicroRNA-373 promotes the development of esophageal squamous cell carcinoma by targeting LATS2 and OXR1. Int J Biol Markers. 2019b;34(2):148–55.

    Article  PubMed  CAS  Google Scholar 

  • Wang Y, Hu Y, Guo J, Wang L. miR-148a-3p suppresses the proliferation and invasion of esophageal cancer by targeting DNMT1. Gen Testing Mol Biomark. 2019c;23(2):98–104.

    Article  CAS  Google Scholar 

  • Wang J, Wu M, Zheng D, Zhang H, Lv Y, Zhang L, et al. Garcinol inhibits esophageal cancer metastasis by suppressing the p300 and TGF-β1 signaling pathways. Acta Pharmacol Sinica. 2020;41(1):82–92.

    Article  Google Scholar 

  • Wang H, DeFina SM, Bajpai M, Yan Q, Yang L, Zhou Z. DNA methylation markers in esophageal cancer: an emerging tool for cancer surveillance and treatment. Am J Cancer Res. 2021a;11(11):5644.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Wang J, Chen Y, Wu R, Lin Y. Circular RNA hsa_circ_0000554 promotes progression and elevates radioresistance through the miR-485-5p/fermitin family members 1 axis in esophageal cancer. Anti-Cancer Drugs. 2021b;32(4):405–16.

    Article  PubMed  CAS  Google Scholar 

  • Wang L, Ji XB, Wang LH, Xia ZK, Xie YX, Liu WJ, et al. MiRNA-30e downregulation increases cancer cell proliferation, invasion and tumor growth through targeting RPS6KB1. Aging (Albany NY). 2021c;13(21):24037.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wang X, Kutschat AP, Yamada M, Prokakis E, Böttcher P, Tanaka K, et al. Bromodomain protein BRDT directs ΔNp63 function and super-enhancer activity in a subset of esophageal squamous cell carcinomas. Cell Death Diff. 2021d;28(7):2207–20.

    Article  CAS  Google Scholar 

  • Wang X, Liu H, Zhang Q, Zhang X, Qin Y, Zhu G, et al. LINC00514 promotes lipogenesis and tumor progression in esophageal squamous cell carcinoma by sponging miR-378a-5p to enhance SPHK1 expression. Int J Oncol. 2021e;59(5):1–16.

    Article  CAS  Google Scholar 

  • Wang W, Dai Y, Yang X, Xiong X. Long non-coding RNA TRPM2 antisense RNA as a potential therapeutic target promotes tumorigenesis and metastasis in esophageal cancer. Bioengineered. 2022;13(2):4397–410.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wapenaar H, Dekker FJ. Histone acetyltransferases: challenges in targeting bi-substrate enzymes. Clin Epigen. 2016;8(1):1–11.

    Article  Google Scholar 

  • Weidle UH, Nopora A. Long non-coding RNAs sponging microRNAs with efficacy in preclinical in vivo models of esophageal squamous cell cancer. Anti Res. 2022;42(7):3233–49.

    CAS  Google Scholar 

  • Wen N, Guo B, Zheng H, Xu L, Liang H, Wang Q, et al. Bromodomain inhibitor jq1 induces cell cycle arrest and apoptosis of glioma stem cells through the VEGF/PI3K/AKT signaling pathway. Int J Oncol. 2019;55(4):879–95.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Wu Y, Sang M, Liu F, Zhang J, Li W, Li Z, et al. Epigenetic modulation combined with PD-1/PD-L1 blockade enhances immunotherapy based on MAGE-A11 antigen-specific CD8+ T cells against esophageal carcinoma. Carcinogenesis. 2020;41(7):894–903.

    Article  PubMed  CAS  Google Scholar 

  • Wu K, Wang Z, Huang Y, Yao L, Kang N, Ge W, et al. LncRNA PTPRG-AS1 facilitates glycolysis and stemness properties of esophageal squamous cell carcinoma cells through miR-599/PDK1 axis. J Gastroenterol Hepatol. 2022a;37(3):507–17.

    Article  PubMed  CAS  Google Scholar 

  • Wu Q, Liu F, Ge M, Laster KV, Wei L, Du R, et al. BRD4 drives esophageal squamous cell carcinoma growth by promoting RCC2 expression. Oncogene. 2022b;41(3):347–60.

    Article  PubMed  CAS  Google Scholar 

  • Wu Q, Zhang H, Yang D, Min Q, Wang Y, Zhang W, Zhan Q. The m6A-induced lncRNA CASC8 promotes proliferation and chemoresistance via upregulation of hnRNPL in esophageal squamous cell carcinoma. Int J Biol Sci. 2022c;18(13):4824–36.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wu Y, Liang Y, Li M, Zhang H. Knockdown of long non-coding RNA SNHG8 suppresses the progression of esophageal cancer by regulating miR-1270/BACH1 axis. Bioengineered. 2022d;13(2):3384–94.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Xi Y, Lin Y, Guo W, Wang X, Zhao H, Miao C, et al. Multi-omic characterization of genome-wide abnormal DNA methylation reveals diagnostic and prognostic markers for esophageal squamous-cell carcinoma. Signal Trans Target Ther. 2022;7(1):53.

    Article  CAS  Google Scholar 

  • Xia W, Qiu M, Chen R, Wang S, Leng X, Wang J, et al. Circular RNA has_circ_0067934 is upregulated in esophageal squamous cell carcinoma and promoted proliferation. Sci Rep. 2016;6(1):1–9.

    Article  Google Scholar 

  • Xiao Y, Su M, Ou W, Wang H, Tian B, Ma J, et al. Involvement of noncoding RNAs in epigenetic modifications of esophageal cancer. Biomed Pharm. 2019;117:109192.

    Article  CAS  Google Scholar 

  • Xie ZF, Li HT, Xie SH, Ma M. Circular RNA hsa_circ_0006168 contributes to cell proliferation, migration and invasion in esophageal cancer by regulating miR-384/RBBP7 axis via activation of S6K/S6 pathway. Eur Rev Med Pharmacol Sci. 2020;24(1):151–63.

    PubMed  Google Scholar 

  • Xiong S, Zheng Y, Jiang P, Liu R, Liu X, Chu Y. MicroRNA-7 inhibits the growth of human non-small cell lung cancer A549 cells through targeting BCL-2. Int J Biol Sci. 2011;7(6):805.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Xiong JX, Wang YS, Sheng J, Xiang D, Huang TX, Tan BB, et al. Epigenetic alterations of a novel antioxidant gene SLC22A3 predispose susceptible individuals to increased risk of esophageal cancer. Int J Biol Sci. 2018;14(12):1658.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Xu H, Ye Y. LINC00488 stimulates the progression of esophageal cancer by targeting microRNA-485-5p. Oncol Lett. 2021;21(2):1–1.

    Google Scholar 

  • Xu C, Yu Y, Ding F. Microarray analysis of circular RNA expression profiles associated with gemcitabine resistance in pancreatic cancer cells. Oncol Rep. 2018a;40(1):395–404.

    PubMed  CAS  Google Scholar 

  • Xu J, Shu Y, Xu T, Zhu W, Qiu T, Li J, et al. Microarray expression profiling and bioinformatics analysis of circular RNA expression in lung squamous cell carcinoma. Am J Trans Res. 2018b;10(3):771.

    CAS  Google Scholar 

  • Xue XJ, Li FR, Yu J. Mitochondrial pathway of the lysine demethylase 5C inhibitor CPI-455 in the Eca-109 esophageal squamous cell carcinoma cell line. W J Gastroenterol. 2021;27(16):1805.

    Article  CAS  Google Scholar 

  • Yan W, Herman JG, Guo M. Epigenome-based personalized medicine in human cancer. Epigenomics. 2016;8(1):119–33.

    Article  PubMed  CAS  Google Scholar 

  • Yan W, Tao M, Jiang B, Yao M, Jun Y, Dai W, et al. Overcoming drug resistance in colon cancer by aptamer-mediated targeted co-delivery of drug and siRNA using grapefruit-derived nanovectors. Cell Physiol Biochem. 2018;50(1):79–91.

    Article  PubMed  CAS  Google Scholar 

  • Yang XJ, Seto E. Lysine acetylation: codified crosstalk with other posttranslational modifications. Mol Cell. 2008;31(4):449–61.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yang C, Yuan W, Yang X, Li P, Wang J, Han J, et al. Circular RNA circ-ITCH inhibits bladder cancer progression by sponging miR-17/miR-224 and regulating p21 PTEN expression. Mol Cancer. 2018;17(1):1–12.

    Article  Google Scholar 

  • Yang YM, Hong P, Xu WW, He QY, Li B. Advances in targeted therapy for esophageal cancer. Signal Trans Target Ther. 2020;5(1):229.

    Article  CAS  Google Scholar 

  • Yang S, Li X, Shen W, Hu H, Li C, Han G. MicroRNA-140 represses esophageal cancer progression via targeting ZEB2 to regulate Wnt/β-catenin pathway. J Surg Res. 2021;257:267–77.

    Article  PubMed  CAS  Google Scholar 

  • Yang J, Zhang Q, Zhao P, Qiao T, Cao Z, Gao F, et al. DNA methyltransferase 3 beta regulates promoter methylation of microRNA-149 to augment esophageal squamous cell carcinoma development through the ring finger protein 2/Wnt/β-catenin axis. Bioengineered. 2022a;13(2):4010–27.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yang WQ, Liang R, Gao MQ, Liu YZ, Qi B, Zhao BS. Inhibition of bromodomain-containing protein 4 enhances the migration of esophageal squamous cell carcinoma cells by inducing cell autophagy. W J Gastrointest Oncol. 2022b;14(12):2340.

    Article  Google Scholar 

  • Yang X, Shen Z, Tian M, Lin Y, Li L, Chai T, et al. LncRNA C9orf139 can regulate the progression of esophageal squamous carcinoma by mediating the miR-661/HDAC11 axis. Trans Oncol. 2022c;24:101487.

    Article  CAS  Google Scholar 

  • Yang Z, Ma R, Li J, Zhao L. Noncoding RNAs in esophageal cancer: a glimpse into implications for therapy resistance. Pharm Res. 2023;106678.

  • You JS, Jones PA. Cancer genetics and epigenetics: two sides of the same coin? Cancer Cell. 2012;22(1):9–20.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yu J, Peng Y, Wu LC, Xie Z, Deng Y, Hughes T, et al. Curcumin down-regulates DNA methyltransferase 1 and plays an anti-leukemic role in acute myeloid leukemia. PloS One. 2013;8(2):e55934.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yu X, Jiang X, Li H, Guo L, Jiang W, Lu SH. miR-203 inhibits the proliferation and self-renewal of esophageal cancer stem-like cells by suppressing stem renewal factor Bmi-1. Stem Cells Dev. 2014;23(6):576–85.

    Article  PubMed  CAS  Google Scholar 

  • Yuan J, Jiang Q, Gong T, Fan D, Zhang J, Chen F, et al. Loss of grand histone H3 lysine 27 trimethylation domains mediated transcriptional activation in esophageal squamous cell carcinoma. NPJ Genom Med. 2021;6(1):65.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zare M, Jazii FR, Alivand MR, Nasseri NK, Malekzadeh R, Yazdanbod M. Qualitative analysis of Adenomatous Polyposis Coli promoter: hypermethylation, engagement and effects on survival of patients with esophageal cancer in a high risk region of the world, a potential molecular marker. BMC Cancer. 2009;9(1):1–12.

    Article  Google Scholar 

  • Zengerle M, Chan KH, Ciulli A. Selective small molecule induced degradation of the BET bromodomain protein BRD4. ACS Chem Biol. 2015;10(8):1770–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhang C, Xiang T, Li S, Ye L, Feng Y, Pei L, et al. The novel 19q13 KRAB zinc-finger tumour suppressor ZNF382 is frequently methylated in oesophageal squamous cell carcinoma and antagonises Wnt/β-catenin signalling. Cell Death Dis. 2018;9(5):573.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang L, Zhang Y, Wang Y, Zhao Y, Ding H, Li P. Circular RNAs: functions and clinical significance in cardiovascular disease. Front Cell Dev Biol. 2020a;8:584051.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang S, Zheng F, Zhang L, Huang Z, Huang X, Pan Z, et al. LncRNA HOTAIR-mediated MTHFR methylation inhibits 5-fluorouracil sensitivity in esophageal cancer cells. J Exp Clin Cancer Res. 2020b;39(1):1–13.

    Article  Google Scholar 

  • Zhang X, Lu N, Wang L, Wang Y, Li M, Zhou Y, et al. Circular RNAs and esophageal cancer. Cancer Cell Int. 2020c;20:1–9.

    Google Scholar 

  • Zhang M, Zhang M, Li R, Zhang R, Zhang Y. Melatonin sensitizes esophageal cancer cells to 5-fluorouracil via promotion of apoptosis by regulating EZH2 expression. Oncol Rep. 2021a;45(4):1–1.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Sun Z, Jia J, Du T, Zhang N, Tang Y, et al. Overview of histone modification. Histone Mutat Cancer. 2021b:1–16.

  • Zhang W, Zhang L, Cai XJ, Li D, Cao FJ, Zuo ZG, et al. Dexmedetomidine inhibits the growth and metastasis of esophageal cancer cells by down-regulation of lncRNA MALAT1. Kaohsiung J Med Sci. 2022a;38(6):585–93.

    Article  PubMed  CAS  Google Scholar 

  • Zhang X, Wang M, Feng J, Qin B, Zhang C, Zhu C, et al. Multifunctional nanoparticles co-loaded with Adriamycin and MDR-targeting siRNAs for treatment of chemotherapy-resistant esophageal cancer. J Nanobiotechnol. 2022b;20(1):1–18.

    Google Scholar 

  • Zhao R, Casson AG. Epigenetic aberrations and targeted epigenetic therapy of esophageal cancer. Curr Cancer Drug Target. 2008;8(6):509–21.

    Article  CAS  Google Scholar 

  • Zheng R, Liu Y, Zhang X, Zhao P, Deng Q. miRNA-200c enhances radiosensitivity of esophageal cancer by cell cycle arrest and targeting P21. Biomed Pharm. 2017;90:517–23.

    Article  CAS  Google Scholar 

  • Zheng B, Wu Z, Xue S, Chen H, Zhang S, Zeng T, et al. hsa_circRNA_100873 upregulation is associated with increased lymphatic metastasis of esophageal squamous cell carcinoma. Oncol Lett. 2019;18(6):6836–44.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Zheng YJ, Liang TS, Wang J, Zhao JY, Zhai SN, Yang DK, Wang LD. Long non-coding RNA ZNF667-AS1 retards the development of esophageal squamous cell carcinoma via modulation of microRNA-1290-mediated PRUNE2. Trans Oncol. 2022;21:101371.

    Article  CAS  Google Scholar 

  • Zhong L, Zhou S, Tong R, Shi J, Bai L, Zhu Y, et al. Preclinical assessment of histone deacetylase inhibitor quisinostat as a therapeutic agent against esophageal squamous cell carcinoma. Invest New Drugs. 2019;37(4):616–24.

    Article  PubMed  CAS  Google Scholar 

  • Zhou M, Li Y, Lin S, Chen Y, Qian Y, Zhao Z, Fan H. H3K9me3, H3K36me3, and H4K20me3 expression correlates with patient outcome in esophageal squamous cell carcinoma as epigenetic markers. Digest Dis Sci. 2019;64:2147–57.

    Article  PubMed  CAS  Google Scholar 

  • Zhou S, Zhang S, Wang L, Huang S, Yuan Y, Yang J, et al. BET protein inhibitor JQ1 downregulates chromatin accessibility and suppresses metastasis of gastric cancer via inactivating RUNX2/NID1 signaling. Oncogenesis. 2020;9(3):33.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhou X, You M, Wang F, Wang Z, Gao X, Jing C, et al. Multifunctional graphdiyne–cerium oxide nanozymes facilitate microRNA delivery and attenuate tumor hypoxia for highly efficient radiotherapy of esophageal cancer. Adv Mater. 2021;33(24):2100556.

    Article  CAS  Google Scholar 

  • Zhou W, Zhu H, Xu Y, Gu L, Wu W, Zhang Y, et al. miR-498/DNMT3b axis mediates resistance to radiotherapy in esophageal cancer cells. Cancer Biother Radiopharm. 2022;37(4):287–99.

    PubMed  CAS  Google Scholar 

  • Zhu J, Ling Y, Xu Y, Lu MZ, Liu YP, Zhang CS. Elevated expression of MDR1 associated with Line-1 hypomethylation in esophageal squamous cell carcinoma. Int J Clin Exp Pathol. 2015;8(11):14392.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Zhu Y, Yuan T, Zhang Y, Shi J, Bai L, Duan X, et al. AR-42: A pan-HDAC inhibitor with antitumor and antiangiogenic activities in esophageal squamous cell carcinoma. Drug Des Dev Ther. 2019;13:4321.

    Article  CAS  Google Scholar 

  • Zhu X, Liao Y, Tang L. Targeting BRD9 for cancer treatment: a new strategy. OncoTargets Ther. 2020;13:13191.

    Article  CAS  Google Scholar 

  • Zhu L, Li X, Yuan Y, Dong C, Yang M. APC promoter methylation in gastrointestinal cancer. Front Oncol. 2021a;11:653222.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhu ZJ, Pang Y, Jin G, Zhang HY, Wang WH, Liu JW, et al. Hypoxia induces chemoresistance of esophageal cancer cells to cisplatin through regulating the lncRNA-EMS/miR-758-3p/WTAP axis. Aging (Albany NY). 2021b;13(13):17155.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zoppi V, Hughes SJ, Maniaci C, Testa A, Gmaschitz T, Wieshofer C, et al. Iterative design and optimization of initially inactive proteolysis targeting chimeras (PROTACs) identify VZ185 as a potent, fast, and selective von Hippel–Lindau (VHL) based dual degrader probe of BRD9 and BRD7. J Med Chem. 2018;62(2):699–726.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Genetics, Maharshi Dayanand University, (Haryana), Rohtak, 124001, India

    Parul Ahuja, Ritu Yadav, Chetna Yadav & Shalu Ranga

  2. Department of Internal Medicine, Pt. B.D, Sharma University of Health Sciences, (Haryana), Rohtak, 124001, India

    Sandeep Goyal

  3. Department of Dermatology, School of Medicine, Indiana University, Indianapolis, Indiana, 46202, USA

    Lokesh Kadian

Authors
  1. Parul Ahuja
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ritu Yadav
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sandeep Goyal
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chetna Yadav
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shalu Ranga
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lokesh Kadian
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Parul Ahuja, Ritu Yadav, and Sandeep Goyal. The first draft of the manuscript was written by Parul Ahuja, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Ritu Yadav.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ahuja, P., Yadav, R., Goyal, S. et al. Targeting epigenetic deregulations for the management of esophageal carcinoma: recent advances and emerging approaches. Cell Biol Toxicol 39, 2437–2465 (2023). https://doi.org/10.1007/s10565-023-09818-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10565-023-09818-5

Keywords

Search

Navigation