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Current Genomics

Editor-in-Chief

ISSN (Print): 1389-2029
ISSN (Online): 1875-5488

Research Article

Analysis of the Expression of PRDX6 in Patients with Hepatocellular Carcinoma and its Effect on the Phenotype of Hepatocellular Carcinoma Cells

Author(s): Runhong Mu, Mingzhu Chang, Chuanbo Feng, Yunhe Cui, Tingyu Li, Chang Liu, Yilin Wang and Xiao Guo*

Volume 25, Issue 1, 2024

Published on: 22 January, 2024

Page: [2 - 11] Pages: 10

DOI: 10.2174/0113892029273682240111052317

Price: $65

Abstract

Objectives: This research aimed to study the expression of PRDX6 mRNA in hepatocellular carcinoma (HCC) and its effect on the prognosis of HCC. Moreover, the effect of PRDX6 gene knockdown on the proliferation, migration, and invasion of HepG2 cells mediated by lentivirus was also examined. This study offers a theoretical and experimental basis for further research on the mechanism of PRDX6 in liver cancer and new methods for clinical diagnosis and treatment.

Methods: RNA sequence data of 369 HCC patients were screened through the TCGA database, and the expression and clinical characteristics of PRDX6 mRNA were analyzed based on high- -throughput RNA sequencing data. HepG2 cells were divided into WT, sh-NC and sh-PRDX6 groups. Real-time PCR and Western blot were used to detect the expression levels of the PRDX6 gene and protein, respectively. CCK8 method was used to detect the proliferation activity of Hep- G2 cells, scratch healing test was used to detect the migration ability, Transwell chamber was used to detect the invasion ability, and Western blot was used to detect the expression levels of PI3K/Akt/mTOR signaling pathway and Notch signaling pathway-related proteins.

Results: The expression of PRDX6 was significantly correlated with the gender, race, clinical stage, histological grade, and survival time of HCC patients (P < 0.05). Compared with that in WT and sh-NC groups, the expression level of PRDX6 protein in HCC patients was significantly lower (P < 0.01), the proliferation activity of HCC cells was significantly decreased (P < 0.05), and the migration and invasion ability was significantly decreased (P < 0.05) in the sh-PRDX6 group. The expression levels of PI3K, p-Akt, p-mTOR, Notch1, and Hes1 proteins in the sh- PRDX6 group were significantly lower than those in WT and sh-NC groups (P < 0.05).

Conclusion: The expression of PRDX6 may be closely related to the prognosis of HCC. Lentivirus- mediated PRDX6 knockdown can inhibit the proliferation, migration and invasion of HCC cells, which may be related to its regulating the PI3K/Akt/mTOR and Notch1 signaling pathways. PRDX6 is expected to be a new target for the diagnosis and treatment of liver cancer.

Keywords: Hepatocellular carcinoma (HCC), peroxiredoxin 6 (PRDX6), lentivirus, gene knockdown, phenotype, RNA sequence data.

Graphical Abstract
[1]
Bai, D.S.; Zhang, C.; Chen, P.; Jin, S.J.; Jiang, G.Q. The prognostic correlation of AFP level at diagnosis with pathological grade, progression, and survival of patients with hepatocellular carcinoma. Sci. Rep., 2017, 7(1), 12870.
[http://dx.doi.org/10.1038/s41598-017-12834-1] [PMID: 28993684]
[2]
Zheng, R.; Qu, C.; Zhang, S.; Zeng, H.; Sun, K.; Gu, X.; Xia, C.; Yang, Z.; Li, H.; Wei, W.; Chen, W.; He, J. Liver cancer incidence and mortality in China: Temporal trends and projections to 2030. Chin. J. Cancer Res., 2018, 30(6), 571-579.
[http://dx.doi.org/10.21147/j.issn.1000-9604.2018.06.01] [PMID: 30700925]
[3]
Likhitsup, A.; Parikh, N.D. Economic implications of hepatocellular carcinoma surveillance and treatment: A guide for clinicians. PharmacoEconomics, 2020, 38(1), 5-24.
[http://dx.doi.org/10.1007/s40273-019-00839-9] [PMID: 31573053]
[4]
Zhou, J.; Sun, H.C.; Wang, Z.; Cong, W.M.; Wang, J.H.; Zeng, M.S.; Yang, J.M.; Bie, P.; Liu, L.X.; Wen, T.F.; Han, G.H.; Wang, M.Q.; Liu, R.B.; Lu, L.G.; Ren, Z.G.; Chen, M.S.; Zeng, Z.C.; Liang, P.; Liang, C.H.; Chen, M.; Yan, F.H.; Wang, W.P.; Ji, Y.; Cheng, W.W.; Dai, C.L.; Jia, W.D.; Li, Y.M.; Li, Y.X.; Liang, J.; Liu, T.S.; Lv, G.Y.; Mao, Y.L.; Ren, W.X.; Shi, H.C.; Wang, W.T.; Wang, X.Y.; Xing, B.C.; Xu, J.M.; Yang, J.Y.; Yang, Y.F.; Ye, S.L.; Yin, Z.Y.; Zhang, B.H.; Zhang, S.J.; Zhou, W.P.; Zhu, J.Y.; Liu, R.; Shi, Y.H.; Xiao, Y.S.; Dai, Z.; Teng, G.J.; Cai, J.Q.; Wang, W.L.; Dong, J.H.; Li, Q.; Shen, F.; Qin, S.K.; Fan, J. Guidelines for diagnosis and treatment of primary liver cancer in china (2017 Edition). Liver Cancer, 2018, 7(3), 235-260.
[http://dx.doi.org/10.1159/000488035] [PMID: 30319983]
[5]
Zheng, M.; Sun, H.; Tian, Z. Natural killer cells in liver diseases. Front. Med., 2018, 12(3), 269-279.
[http://dx.doi.org/10.1007/s11684-018-0621-4] [PMID: 29675689]
[6]
Chen, V.L.; Sharma, P. Role of biomarkers and biopsy in hepatocellular carcinoma. Clin. Liver Dis., 2020, 24(4), 577-590.
[http://dx.doi.org/10.1016/j.cld.2020.07.001] [PMID: 33012446]
[7]
Sharapov, M.G.; Fesenko, E.E.; Novoselov, V.I. The role of peroxiredoxins in various diseases caused by oxidative stress and the prospects of using exogenous peroxiredoxins. Biophysics, 2018, 63(4), 576-589.
[http://dx.doi.org/10.1134/S0006350918040164]
[8]
Fisher, A.B. Peroxiredoxin 6: A bifunctional enzyme with glutathione peroxidase and phospholipase A2 activities. Antioxid Redox Signal. Antioxid. Redox Signal., 2011, 15(3), 831-844.
[http://dx.doi.org/10.1089/ars.2010.3412] [PMID: 20919932]
[9]
Kim, K.H.; Lee, W.; Kim, E.E. Crystal structures of human peroxiredoxin 6 in different oxidation states. Biochem. Biophys. Res. Commun., 2016, 477(4), 717-722.
[http://dx.doi.org/10.1016/j.bbrc.2016.06.125] [PMID: 27353378]
[10]
Liu, N.N.; Liu, Z.S.; Lu, S.Y.; Hu, P.; Li, Y.S.; Feng, X.L.; Zhang, S.Y.; Wang, N.; Meng, Q.F.; Yang, Y.J.; Tang, F.; Xu, Y.M.; Zhang, W.H.; Guo, X.; Chen, X.F.; Zhou, Y.; Ren, H.L. Full-length cDNA cloning, molecular characterization and differential expression analysis of peroxiredoxin 6 from Ovis aries. Vet. Immunol. Immunopathol., 2015, 164(3-4), 208-219.
[http://dx.doi.org/10.1016/j.vetimm.2015.01.006] [PMID: 25712755]
[11]
Raatikainen, S.; Aaaltomaa, S.; Kärjä, V.; Soini, Y. Increased peroxiredoxin 6 expression predicts biochemical recurrence in prostate cancer patients after radical prostatectomy. Anticancer Res., 2015, 35(12), 6465-6470.
[PMID: 26637857]
[12]
Wen-Shih, H. Expression of prdx6 correlates with migration and invasiveness of colorectal cancer cells. Cell. Physiol. Biochem., 2018, 2616-2630.
[13]
Hu, X.; lu, E.; Pan, C.; Xu, Y.; Zhu, X. Overexpression and biological function of PRDX6 in human cervical cancer. J. Cancer, 2020, 11(9), 2390-2400.
[http://dx.doi.org/10.7150/jca.39892] [PMID: 32201510]
[14]
Gu, C.; Chang, W.; Wu, J.; Yao, Y.; Liu, G.; Yuan, Y.; Quan, W.; Sun, Z.; Shang, A.; Li, D. NCOA4: An immunomodulation-related prognostic biomarker in colon adenocarcinoma and pan-cancer. J. Oncol., 2022, 2022, 1-24.
[http://dx.doi.org/10.1155/2022/5242437] [PMID: 35756082]
[15]
Hu, B.; Wei, Q.; Li, X.; Ju, M.; Wang, L.; Zhou, C.; Chen, L.; Li, Z.; Wei, M.; He, M.; Zhao, L. Development of an IFNγ response-related signature for predicting the survival of cutaneous melanoma. Cancer Med., 2020, 9(21), 8186-8201.
[http://dx.doi.org/10.1002/cam4.3438] [PMID: 32902917]
[16]
Shearer, R.F.; Saunders, D.N. Experimental design for stable genetic manipulation in mammalian cell lines: lentivirus and alternatives. Genes Cells, 2015, 20(1), 1-10.
[http://dx.doi.org/10.1111/gtc.12183] [PMID: 25307957]
[17]
Pfaffl, M.W. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res., 2001, 29(9), 45e-45.
[http://dx.doi.org/10.1093/nar/29.9.e45] [PMID: 11328886]
[18]
Knoops, B.; Argyropoulou, V.; Becker, S.; Ferté, L.; Kuznetsova, O. Multiple roles of peroxiredoxins in inflammation. Mol. Cells, 2016, 39(1), 60-64.
[http://dx.doi.org/10.14348/molcells.2016.2341] [PMID: 26813661]
[19]
Nicolussi, A.; D’Inzeo, S.; Capalbo, C.; Giannini, G.; Coppa, A. The role of peroxiredoxins in cancer. Mol. Clin. Oncol., 2017, 6(2), 139-153.
[http://dx.doi.org/10.3892/mco.2017.1129] [PMID: 28357082]
[20]
Li, C.; Wu, J.; He, M. Peroxiredoxin 6 highly expressed in human cervical squamous cell carcinoma. Biomedicine, 2014, (2), 32-35.
[21]
Pak, J.H.; Choi, W.H.; Lee, H.M.; Joo, W.D.; Kim, J.H.; Kim, Y.T.; Kim, Y.M.; Nam, J.H. Peroxiredoxin 6 overexpression attenuates cisplatin-induced apoptosis in human ovarian cancer cells. Cancer Invest., 2011, 29(1), 21-28.
[http://dx.doi.org/10.3109/07357907.2010.535056] [PMID: 21166495]
[22]
Schmitt, A.; Schmitz, W.; Hufnagel, A.; Schartl, M.; Meierjohann, S. Peroxiredoxin 6 triggers melanoma cell growth by increasing arachidonic acid-dependent lipid signalling. Biochem. J., 2015, 471(2), 267-279.
[http://dx.doi.org/10.1042/BJ20141204] [PMID: 26285655]
[23]
Basu, A.; Martinez, S.; Melendez, L. High expression of peroxiredoxins in prostate cancer cells. Cancer Res., 2007, 67, 2911-2911.
[24]
Yun, H.M.; Park, K.R.; Park, M.H.; Kim, D.H.; Jo, M.R.; Kim, J.Y.; Kim, E.C.; Yoon, D.Y.; Han, S.B.; Hong, J.T. PRDX6 promotes tumor development via the JAK2/STAT3 pathway in a urethane-induced lung tumor model. Free Radic. Biol. Med., 2015, 80, 136-144.
[http://dx.doi.org/10.1016/j.freeradbiomed.2014.12.022] [PMID: 25582888]
[25]
Karihtala, P.; Mäntyniemi, A.; Kang, S.W.; Kinnula, V.L.; Soini, Y. Peroxiredoxins in breast carcinoma. Clin. Cancer Res., 2003, 9(9), 3418-3424.
[PMID: 12960131]
[26]
Xu, J.; Su, Q.; Gao, M.; Liang, Q.; Li, J.; Chen, X. Differential expression and effects of peroxiredoxin-6 on drug resistance and cancer stem cell-like properties in non-small cell lung cancer. OncoTargets Ther., 2019, 12, 10477-10486.
[http://dx.doi.org/10.2147/OTT.S211125] [PMID: 31819528]
[27]
Quan, C.; Cha, E.J.; Lee, H.L.; Han, K.H.; Lee, K.M.; Kim, W.J. Enhanced expression of peroxiredoxin I and VI correlates with development, recurrence and progression of human bladder cancer. J. Urol., 2006, 175(4), 1512-1516.
[http://dx.doi.org/10.1016/S0022-5347(05)00659-2] [PMID: 16516038]
[28]
a) Chang, X.Z.; Li, D.Q.; Hou, Y.F.; Wu, J.; Lu, J.S.; Di, G.H.; Jin, W.; Ou, Z.L.; Shen, Z.Z.; Shao, Z.M. Identification of the functional role of peroxiredoxin 6 in the progression of breast cancer. Breast Cancer Res., 2007, 9(6), R76.
[http://dx.doi.org/10.1186/bcr1789] [PMID: 17980029];
b) He, Y.; Xu, W.; Xiao, Y.; Pan, L.; Chen, G.; Tang, Y.; Zhou, J.; Wu, J.; Zhu, W.; Zhang, S.; Cao, J. Overexpression of peroxiredoxin 6 (PRDX6) promotes the aggressive phenotypes of esophageal squamous cell carcinoma. J. Cancer, 2018, 9(21), 3939-3949.
[http://dx.doi.org/10.7150/jca.26041]
[29]
Law, N.C.; White, M.F.; Hunzicker-Dunn, M.E. G protein-coupled receptors (GPCRs) that signal via Protein Kinase A (PKA) Cross-talk at Insulin Receptor Substrate 1 (IRS1) to activate the phosphatidylinositol 3-kinase (PI3K)/AKT pathway. J. Biol. Chem., 2016, 291(53), 27160-27169.
[http://dx.doi.org/10.1074/jbc.M116.763235] [PMID: 27856640]
[30]
Li, C.; Song, G.; Zhang, S.; Wang, E.; Cui, Z. Wnt3a increases the metastatic potential of non-small cell lung cancer cells in vitro in part via its upregulation of Notch3. Oncol. Rep., 2015, 33(3), 1207-1214.
[http://dx.doi.org/10.3892/or.2014.3700] [PMID: 25572698]
[31]
Spitschak, A.; Meier, C.; Kowtharapu, B.; Engelmann, D.; Pützer, B.M. MiR-182 promotes cancer invasion by linking RET oncogene activated NF-κB to loss of the HES1/Notch1 regulatory circuit. Mol. Cancer, 2017, 16(1), 24.
[http://dx.doi.org/10.1186/s12943-016-0563-x] [PMID: 28122586]

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