Abstract：Objective This study was designed to investigate the effect of Decitabine (DAC) on hepatocellular carcinoma cell migration and invasion and to explore its molecular mechanisms. Methods MTT assay was used to detect the effect of different concentrations of DAC on the viability of hepatocellular carcinoma MHCC97H cells. The influence of different concentrations of DAC on the migratory and invasive abilities of hepatocellular carcinoma MHCC97H cells were determined by cell wound healing and transwell invasion assays. The impact of DAC on the protein expression of suppressor of cytokine signaling 1(SOCS1) in hepatocellular carcinoma MHCC97H and SK-Hep-1 cells was assessed by Western blot (WB). The siRNA transfection assay was performed to knock down the expression of SOCS1 in hepatocellular carcinoma MHCC97H cells, and changes in the migratory and invasive ability of cells were observed. Results DAC inhibited the viability of hepatocellular carcinoma MHCC97H cells in a concentration-dependent manner (IC50=5.0 μM) and had the inhibitory effect on cell migration and invasion. Knocking down the expression of SOCS1 enhanced the migration and invasion of hepatocellular carcinoma MHCC97H cells. DAC upregulated the expression of SOCS1 in hepatocellular carcinoma cells (MHCC97H and SK-Hep-1) in a concentration-dependent manner, and DAC reversed the promotion of migration and invasion of hepatocellular carcinoma MHCC97H cells by low expression of SOCS1. Conclusion DAC inhibits migration and invasion of hepatocellular carcinoma cells by upregulating SOCS1 expression.
[1] MCGLYNN KA, PETRICK JL, EL-SERAG HB.Epidemiology of hepatocellular carcinoma[J]. Hepatology, 2021, 73(S1): 4-13. [2] MITTAL S, EL-SERAG HB, SADA YH, et al. Hepatocellular carcinoma in the absence of cirrhosis in United States veterans is associated with nonalcoholic fatty liver disease[J]. Clin Gastroenterol Hepatol, 2016, 14(1): 124-131. e1. [3] GANESAN P, KULIK LM.Hepatocellular Carcinoma: New Developments[J]. Clin Liver Dis, 2023, 27(1): 85-102. [4] PASHA HF, MOHAMED RH, RADWAN MI.RASSF1A and SOCS1 genes methylation status as a noninvasive marker for hepatocellular carcinoma[J]. Cancer Biomark, 2019, 24(2): 241-247. [5] YOSHIKAWA H, MATSUBARA K, QIAN GS, et al.SOCS-1, a negative regulator of the JAK/STAT pathway, is silenced by methylation in human hepatocellular carcinoma and shows growth-suppression activity[J]. Nat Genet, 2001, 28: 29-35. [6] SIEGEL RL, MILLER KD, WAGLE NS, et al.Cancer statistics, 2023[J]. CA Cancer J Clin, 2023, 73(1): 17-48. [7] SORM F, PÍSKALA A, CIHÁK A, et al.5-Azacytidine, a new, highly effective cancerostatic[J]. Experientia, 1964, 15; 20(4): 202-203. [8] SALAMA BM, HELMY MW, FOUAD H, et al.The Synergistic Antitumor Effect of Decitabine and Vorinostat Combination on HepG2 Human Hepatocellular Carcinoma Cell Line via Epigenetic Modulation of Autophagy-Apoptosis Molecular Crosstalk[J]. Curr Issues Mol Biol, 2023, 45(7): 5935-5949. [9] ZHANG L, LI HT, SHEREDA R, et al.DNMT and EZH2 inhibitors synergize to activate therapeutic targets in hepatocellular carcinoma[J]. Cancer Lett, 2022, 548: 215899. [10] STARR R, WILLSON TA, VINEY EM, et al.A Family of Cytokine-Inducible Inhibitors of Signalling[J]. Nature, 1997, 387: 917-921. [11] ENDO TA, MASUHARA M, YOKOUCHI M, et al.A New Protein Containing an SH2 Domain That Inhibits JAK Kinases[J]. Nature, 1997, 387: 921-924. [12] NAKA T, NARAZAKI M, HIRATA M, et al.Structure and Function of a New STAT-Induced STAT Inhibitor[J]. Nature, 1997, 387: 924-929. [13] MASUZAKI R, KANDA T, SASAKI R, et al.Suppressors of Cytokine Signaling and Hepatocellular Carcinoma[J]. Cancers (Basel), 2022, 14(10): 2549. [14] SHUKLA A, KHAN MGM, CAYARGA AA, et al.The Tumor Suppressor SOCS1 Diminishes Tolerance to Oxidative Stress in Hepatocellular Carcinoma[J]. Cancers (Basel), 2024, 16(2): 292. [15] OKOCHI O, HIBI K, SAKAI M, et al.Methylation-mediated silencing of SOCS-1 gene in hepatocellular carcinoma derived from cirrhosis[J]. Clin Cancer Res, 2003, 9(14): 5295-5298. [16] YOSHIDA T, OGATA H, KAMIO M, et al.SOCS1 is a suppressor of liver fibrosis and hepatitis-induced carcinogenesis[J]. J Exp Med, 2004, 199(12): 1701-1707. [17] KO E, KIM SJ, JOH JW, et al.CpG island hypermethylation of SOCS-1 gene is inversely associated with HBV infection in hepatocellular carcinoma[J]. Cancer Lett, 2008, 271(2): 240-250. [18] YOSHIKAWA H, MATSUBARA K, QIAN GS, et al.SOCS-1, a negative regulator of the JAK/STAT pathway, is silenced by methylation in human hepatocellular carcinoma and shows growth-suppression activity[J]. Nat Genet, 2001, 28(1): 29-35. [19] CABRAL LKD, REYES PAC, CROCÈ LS, et al.The Relevance of SOCS1 Methylation and Epigenetic Therapy in Diverse Cell Populations of Hepatocellular Carcinoma[J]. Diagnostics (Basel), 2021, 11(10): 1825.
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