沉默PRMT5基因对人肝癌细胞生物学行为的影响

doi:10.11904/j.issn.1002-3070.2020.03.004

Abstract

Abstract: Objective To investigate the effect of protein arginine methyltransferase 5(PRMT5)on the biological behavior of human hepatocellular carcinoma cells.Methods The expression of PRMT5 was detected with Western blot in normal liver cell line LO2 and hepatocellular carcinoma cell lines HepG2 and Huh7 cells.siRNA technology was used to knockdown the expression of PRMT5 and flow cytometry was used to detect the apoptosis of HepG2 and Huh7 cells.The protein expression of protein kinase B(AKT)and phosphorylated protein kinase B(P-AKT)was detected by Western blot.Results Compared with LO2 cells,PRMT5 was highly expressed in hepatocellular carcinoma cell lines HepG2 and Huh7(P＜0.05).Inhibition of PRMT5 expression could promote apoptosis of HCC cells.The expression of P-AKT was decreased when knocked-down the expression of PRMT5 gene(P＜0.01).Conclusion PRMT5 may promote HCC(Hepatocellular Carcinoma)cell apoptosis by regulating AKT pathway.Therefore,PRMT5 may be a potential biomarker and promising therapeutic target for hepatocellular carcinoma.

Key words: PRMT5, Hepatocellular carcinoma cells, P-AKT

CLC Number:

R735.7

ZHOU Jian,CHEN Xuejian,WANG Wei,LI Ning,SUN Zhenyu,XU Lishan. The effect of silencing PRMT5 gene in biological behavior of human hepatocellular carcinoma cells[J]. Journal of Practical Oncology, 2020, 34(3): 208-213.

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URL: http://journal09.magtechjournal.com/Jwk3_syzlxzz/EN/10.11904/j.issn.1002-3070.2020.03.004

http://journal09.magtechjournal.com/Jwk3_syzlxzz/EN/Y2020/V34/I3/208

References

1 Hlady RA,Zhao X,Pan X,et al.Genome-wide discovery and validation of diagnostic DNA methylation-based biomarkers for hepatocellular cancer detection in circulating cell free DNA[J].Theranostics,2019,9(24):7239-7250.
2 Li Z,Zhang J,Liu X,et al.The LINC01138 drives malignancies via activating arginine methyltransferase 5 in hepatocellular carcinoma[J].Nat Commun,2018,9(1):1572.
3 Siegel RL,Miller KD,Jemal A.Cancer statistics[J].CA Cancer J Clin,2017,67(1):7-30.
4 Singal AG,El-Serag HB.Hepatocellular carcinoma from epidemiology to prevention:translating knowledge into practice[J].Clin Gastroenterol Hepatol,2015,13(12):2140-2151.
5 文娟娟,瞿冰,刘超.肝癌组织中抗凝血酶III基因表达的临床意义[J].实用肿瘤学杂志,2018,32(2):117-121.
6 Yang H,Zhao X,Zhao L,et al.PRMT5 competitively binds to CDK4 to promote G1-S transition upon glucose induction in hepatocellular carcinoma[J].Oncotarget,2016,7(44):72131-72147.
7 El-Serag HB,Marrero JA,Rudolph L,et al.Diagnosis and treatment of hepatocellular carcinoma[J].Gastroenterology,2008,134(6):1752-1763.
8 Toh TB,Lim JJ,Hooi L,et al.Targeting Jak/Stat pathway as a therapeutic strategy against SP/CD44+ tumorigenic cells in Akt/β-catenin-driven hepatocellular carcinoma[J].J Hepatol,2020,72(1):104-118.
9 Liu L,Zhao X,Zhao L,et al.Arginine Methylation of SREBP1a via PRMT5 promotes de novo lipogenesis and tumor growth[J].Cancer Res,2016,76(5):1260-1272.
10 Zhang B,Dong S,Li Z,et al.Targeting protein arginine methyltransferase 5 inhibits human hepatocellular carcinoma growth via the downregulation of beta-catenin[J].J Transl Med,2015,13(1):349.
11 Yang H,Zhao X,Zhao L,et al.PRMT5 competitively binds to CDK4 to promote G1-S transition upon glucose induction in hepatocellular carcinoma[J].Oncotarget,2016,7(44):72131-72147.
12 Gu Z,Gao S,Zhang F,et al.Protein arginine methyltransferase 5 is essential for growth of lung cancer cells[J].Biochem J,2012,446(2):235-241.
13 Li Y,Yang Y,Liu X,et al.PRMT5 Promotes human lung cancer cell apoptosis via Akt/Gsk3β signaling induced by resveratrol[J].Cell Transplant,2019,28(12):1664-1673.
14 Powers MA,Fay MM,Factor RE,et al.Protein arginine methyltransferase 5 accelerates tumor growth by arginine methylation of the tumor suppressor programmed cell death 4[J].Cancer Res,2011,71(16):5579-5587.
15 Ibrahim R,Matsubara D,Osman W,et al.Expression of PRMT5 in lung adenocarcinoma and its significance in epithelial-mesenchymal transition[J].Hum Pathol,2014,45(7):1397-1405.
16 Liu F,Zhao X,Perna F,et al.JAK2V617F-mediated phosphorylation of PRMT5 downregulates its methyltransferase activity and promotes myeloproliferation[J].Cancer Cell,2011,19(2):283-294.
17 Yan F,Alinari L,Lustberg ME,et al.Genetic validation of the protein arginine methyltransferase PRMT5 as a candidate therapeutic target in glioblastoma[J].Cancer Res,2014,74(6):1752-1765.
18 Jansson M,Durant ST,Cho EC,et al.Arginine methylation regulates the p53 response[J].Nat Cell Biol,2008,10(12):1431-1439.
19 Tanaka H,Hoshikawa Y,Oh-hara T,et al.PRMT5,a novel TRAIL receptor-binding protein,inhibits TRAIL-induced apoptosis via nuclear factor-kappaB activation[J].Mol Cancer Res,2009,7(4):557-569.
20 Cho EC,Zheng S,Munro S,et al.Arginine methylation controls growth regulation by E2F-1[J].EMBO J,2012,31(7):1785-1797.
21 Pal S,Baiocchi RA,Byrd JC,et al.Low levels of miR92b/96 induce PRMT5 translation and H3R8/H4R3 methylation in mantle cell lymphoma[J].EMBO J,2007,26(15):3558-3569.
22 Wang L,Pal S,Sif S.Protein arginine methyltransferase 5 suppresses the transcription of the RB family of tumor suppressors in leukemia and lymphoma cells[J].Mol Cell Biol,2008,28(20):6262-6277.
23 Zhang S,Ma Y,Hu X,et al.Targeting PRMT5/Akt signalling axis prevents human lung cancer cell growth[J].J Cell Mol Med,2019,23(2):1333-1342.
24 Jing P,Zhao N,Ye M,et al.Protein arginine methyltransferase 5 promotes lung cancer metastasis via the epigenetic regulation of miR-99 family/FGFR3 signaling[J].Cancer Lett,2018,427:38-48.
25 Gu Z,Li Y,Lee P,et al.Protein arginine methyltransferase 5 functions in opposite ways in the cytoplasm and nucleus of prostate cancer cells[J].PLoS One,2012,7(8):e44033.
26 Wu Z,Lin Y.Long noncoding RNA LINC00515 promotes cell proliferation and inhibits apoptosis by sponging miR-16 and activating PRMT5 expression in human glioma[J].Onco Targets Ther,2019,12:2595-2604.
27 Zhang B,Zhang S,Zhu L,et al.Arginine methyltransferase inhibitor 1 inhibits gastric cancer by downregulating eIF4E and targeting PRMT5[J].Toxicol Appl Pharmacol,2017,336:1-7.
28 Kanda M,Shimizu D,Fujii T,et al.Protein arginine methyltransferase 5 is associated with malignant phenotype and peritoneal metastasis in gastric cancer[J].Int J Oncol,2016,49(3):1195-1202.
29 Zhu K,Peng Y,Hu J,et al.Metadherin-PRMT5 complex enhances the metastasis of hepatocellular carcinoma through the WNT/β-catenin signaling pathway[J].Carcinogenesis,2020,4(2):130-138.

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The effect of silencing PRMT5 gene in biological behavior of human hepatocellular carcinoma cells

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