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The Long Noncoding RNA Gall Bladder Cancer-Associated Suppressor of Pyruvate Carboxylase Inhibits the Proliferation, Migration, and Invasion of Colorectal Cancer Cells and Induces Their Apoptosis

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Abstract

This study aimed to determine the role of the long noncoding RNA (lncRNA) gall bladder cancer-associated suppressor of pyruvate carboxylase (SOD2-1) in the progression of colorectal cancer (CRC). A total of 23 pairs of specimens, including CRC tissues and adjacent normal tissues, were collected, and the expression of lncRNA SOD2-1 (lnc-SOD2-1) was measured. lnc-SOD2-1 function was examined using HCT15 and HCT116 cells. A lnc-SOD2-1 overexpression vector was designed and transfected into both cell lines. MTS and colony formation assays were used to determine cell viability. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling assays were performed to measure apoptosis. Cell migration and invasion were evaluated using the Transwell assay. Migration and invasion markers were validated using quantitative reverse transcription–polymerase chain reaction and western blot analysis. The results indicated that the expression of lnc-SOD2-1 was downregulated in CRC tissues. lnc-SOD2-1 overexpression evidently decreased cell viability and led to the formation of fewer cell colonies. lnc-SOD2-1 overexpression induced ~ twofold higher apoptosis than the control group. lnc-SOD2-1 overexpression reduced the proportion of migratory and invasive cells to 50% and 75% of the control group, respectively. lnc-SOD2-1 overexpression significantly decreased the expression of matrix metalloproteinase-2 and -9. In conclusion, lnc-SOD2-1 may act as a tumor suppressor that inhibits the proliferation, migration, and invasion of CRC cells and induces their apoptosis.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  • Alaseem A et al (2019) Matrix metalloproteinases: a challenging paradigm of cancer management. Semin Cancer Biol 56:100–115

    Article  CAS  PubMed  Google Scholar 

  • Bhan A et al (2017) Long noncoding RNA and cancer: a new paradigm. Cancer Res 77(15):3965–3981

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen S et al (2017) Long non-coding RNA PTENP1 inhibits proliferation and migration of breast cancer cells via AKT and MAPK signaling pathways. Oncol Lett 14(4):4659–4662

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen Y et al (2020) microRNA-499a promotes the progression and chemoresistance of cervical cancer cells by targeting SOX6. Apoptosis 25(3–4):205–216

    Article  CAS  PubMed  Google Scholar 

  • Choi ES et al (2021) CD5L as an extracellular vesicle-derived biomarker for liquid biopsy of lung cancer. Diagnostics (basel) 11(4):620

    Article  CAS  PubMed  Google Scholar 

  • Cowell S et al (2018) Towards an MMP-2-activated molecular agent for cancer imaging. Dalton Trans 47(5):1530–1534

    Article  CAS  PubMed  Google Scholar 

  • Cui D et al (2021) Inhibiting PHD2 in human periodontal ligament cells via lentiviral vector-mediated RNA interference facilitates cell osteogenic differentiation and periodontal repair. J Leukoc Biol 110(3):449–459

    Article  CAS  PubMed  Google Scholar 

  • Dekker E et al (2019) Colorectal cancer. Lancet 394(10207):1467–1480

    Article  PubMed  Google Scholar 

  • El Homsi M et al (2019) Uterine metastasis from invasive ductal breast carcinoma mimicking fibroid features on MRI and detected by FDG PET/CT: role of SUVmax. Eur J Gynaecol Oncol 40(6):1079–1082

    Article  Google Scholar 

  • Fan XJ et al (2013) Snail promotes lymph node metastasis and twist enhances tumor deposit formation through epithelial-mesenchymal transition in colorectal cancer. Hum Pathol 44(2):173–180

    Article  CAS  PubMed  Google Scholar 

  • Ferlay J et al (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127(12):2893–2917

    Article  CAS  PubMed  Google Scholar 

  • Ghafouri-Fard S et al (2021) LncRNA signature in colorectal cancer. Pathol Res Pract 222:153432

    Article  CAS  PubMed  Google Scholar 

  • Gialeli C et al (2011) Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting. FEBS J 278(1):16–27

    Article  CAS  PubMed  Google Scholar 

  • Herszenyi L et al (2012) The behavior of matrix metalloproteinases and their inhibitors in colorectal cancer. Int J Mol Sci 13(10):13240–13263

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hu B et al (2018) CD44 promotes cell proliferation in non-small cell lung cancer. Oncol Lett 15(4):5627–5633

    PubMed  PubMed Central  Google Scholar 

  • Huang H (2018) Matrix metalloproteinase-9 (MMP-9) as a cancer biomarker and MMP-9 biosensors: recent advances. Sensors (basel). https://doi.org/10.3390/s18103249

    Article  PubMed  PubMed Central  Google Scholar 

  • Jablonska-Trypuc A et al (2016) Matrix metalloproteinases (MMPs), the main extracellular matrix (ECM) enzymes in collagen degradation, as a target for anticancer drugs. J Enzyme Inhib Med Chem 31(sup1):177–183

    Article  CAS  PubMed  Google Scholar 

  • Jemal A et al (2008) (2008) Cancer statistics. CA Cancer J Clin 58(2):71–96

    Article  PubMed  Google Scholar 

  • Jensen SA et al (2010) Expression of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinases 1 (TIMP-1) by colorectal cancer cells and adjacent stroma cells-associations with histopathology and patients outcome. Eur J Cancer 46(18):3233–3242

    Article  CAS  PubMed  Google Scholar 

  • Kanthan R et al (2012) Molecular events in primary and metastatic colorectal carcinoma: a review. Patholog Res Int 2012:597497

    PubMed  PubMed Central  Google Scholar 

  • Kogo R et al (2011) Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Res 71(20):6320–6326

    Article  CAS  PubMed  Google Scholar 

  • Kong W et al (2021) LncRNA MCF2L-AS1 aggravates the malignant development of colorectal cancer via targeting miR-105-5p/RAB22A axis. BMC Cancer 21(1):1069

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li L, Ma J (2021) Molecular characterization of metabolic subtypes of gastric cancer based on metabolism-related lncRNA. Sci Rep 11(1):21491

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li J et al (2016) Regulation of lncRNA and its role in cancer metastasis. Oncol Res 23(5):205–217

    Article  PubMed  PubMed Central  Google Scholar 

  • Li Y et al (2021) Integrated bioinformatical analysis of lncRNA-mRNA co-expression profiles of cervical cancer. Clin Exp Obstet Gynecol 48(6):1381–1392

    Article  Google Scholar 

  • Lin F et al (2017) Thioredoxin-1 promotes colorectal cancer invasion and metastasis through crosstalk with S100P. Cancer Lett 401:1–10

    Article  CAS  PubMed  Google Scholar 

  • Liu SJ et al (2021) Long noncoding RNAs in cancer metastasis. Nat Rev Cancer 21(7):446–460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ma MZ et al (2016) Long noncoding RNA GCASPC, a target of miR-17-3p, negatively regulates pyruvate carboxylase-dependent cell proliferation in gallbladder cancer. Cancer Res 76(18):5361–5371

    Article  CAS  PubMed  Google Scholar 

  • Pastushenko I, Blanpain C (2019) EMT transition states during tumor progression and metastasis. Trends Cell Biol 29(3):212–226

    Article  CAS  PubMed  Google Scholar 

  • Reggiardo RE et al (2022) LncRNA biomarkers of inflammation and cancer. Adv Exp Med Biol 1363:121–145

    Article  CAS  PubMed  Google Scholar 

  • Sai C et al (2021) Macleayins a from macleaya promotes cell apoptosis through wnt/β-catenin signaling pathway and inhibits proliferation, migration, and invasion in cervical cancer HeLa cells. Front Pharmacol 12:668348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smolarz B et al (2021) The Role of lncRNA in the development of tumors, including breast cancer. Int J Mol Sci. https://doi.org/10.3390/ijms22168427

    Article  PubMed  PubMed Central  Google Scholar 

  • Valastyan S, Weinberg RA (2011) Tumor metastasis: molecular insights and evolving paradigms. Cell 147(2):275–292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang D et al (2018) Influence of the twist gene on the invasion and metastasis of colon cancer. Oncol Rep 39(1):31–44

    PubMed  Google Scholar 

  • Wang W et al (2019) SMAD specific E3 ubiquitin protein ligase 1 promotes ovarian cancer cell migration and invasion via the activation of the RhoA/ROCK signaling pathway. Oncol Rep 41(1):668–676

    CAS  PubMed  Google Scholar 

  • Wang K et al (2021) Downregulation of DEAD-box helicase 21 (DDX21) inhibits proliferation, cell cycle, and tumor growth in colorectal cancer via targeting cell division cycle 5-like (CDC5L). Bioengineered 12(2):12647–12658

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang D et al (2022) Ganoderic acid A alleviates the degeneration of intervertebral disc via suppressing the activation of TLR4/NLRP3 signaling pathway. Bioengineered 13(5):11684–11693

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weitz J et al (2005) Colorectal cancer. Lancet 365(9454):153–165

    Article  PubMed  Google Scholar 

  • Wong SHM et al (2018) E-cadherin: Its dysregulation in carcinogenesis and clinical implications. Crit Rev Oncol Hematol 121:11–22

    Article  PubMed  Google Scholar 

  • Xu C et al (2011) MALAT-1: a long non-coding RNA and its important 3’ end functional motif in colorectal cancer metastasis. Int J Oncol 39(1):169–175

    PubMed  Google Scholar 

  • Xu LJ et al (2018) LncRNA SNHG7 promotes the proliferation of esophageal cancer cells and inhibits its apoptosis. Eur Rev Med Pharmacol Sci 22(9):2653–2661

    PubMed  Google Scholar 

  • Zhang C et al (2021a) LncRNA DRAIC promotes apoptosis and inhibits proliferation of colorectal cancer via regulating MiR-223. Minerva Med. https://doi.org/10.23736/s0026-4806.21.07605-9

    Article  PubMed  Google Scholar 

  • Zhang H et al (2021b) Long noncoding RNA SNHG10 promotes colorectal cancer cells malignant progression by targeting miR-3690. Bioengineered 12(1):6010–6020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao X et al (2019) TPM4 promotes cell migration by modulating F-actin formation in lung cancer. Onco Targets Ther 12:4055–4063

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zheng J et al (2021) Comprehensive analyses of glycolysis-related lncRNAs for ovarian cancer patients. J Ovarian Res 14(1):124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhong Y et al (2019) Long noncoding RNAs as potential biomarkers and therapeutic targets in gallbladder cancer: a systematic review and meta-analysis. Cancer Cell Int 19:169

    Article  PubMed  PubMed Central  Google Scholar 

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Contributions

Tingting Xie and Jianian Guo conceived and designed the study and drafted the manuscript. Tingting Xie, Jianian Guo, and Wei Wang performed the experiments and analyzed and interpreted the data. Wei Wang critically revised the manuscript and prepared the figures.

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Correspondence to Wei Wang.

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All procedures were performed in accordance with the Declaration of Helsinki. Moreover, this study was approved by the Ethics Committee of the Second Affiliated Hospital of Guangzhou Medical University (Approval number: 2021-KY-ks-02).

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Xie, T., Guo, J. & Wang, W. The Long Noncoding RNA Gall Bladder Cancer-Associated Suppressor of Pyruvate Carboxylase Inhibits the Proliferation, Migration, and Invasion of Colorectal Cancer Cells and Induces Their Apoptosis. Biochem Genet (2024). https://doi.org/10.1007/s10528-024-10786-6

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