miR-9 and miR-181a Target Gab2 to Inhibit the Proliferation and Migration of Hepatocellular Carcinoma HepG2 Cells

Abstract

The incidence of liver cancer ranks seventh globally, with nearly half of all cases occurring in East Asia, but currently, there are very few drugs to treat it. Our previous studies demonstrated that the signal integration protein Gab2 is a potential drug target for the prevention and therapy of liver cancer. Here, we screened for and identified two miRNAs that target Gab2 to suppress the proliferation and migration of hepatocellular carcinoma (HCC) cells. First, we predicted Gab2-targeting miRNAs through biological websites, and we selected nine miRNAs that were reported in the literature as being abnormally expressed in liver cancer and fatty liver tissue. Then, we measured the expression of these miRNAs in the hepatic epithelial cell line HL-7702 and the HCC cell line HepG2. The expression levels of miR-9, miR-181a, miR-181c, miR-34a, and miR-134 were high in HL-7702 cells but low in HepG2 cells, and their expression patterns were the opposite of Gab2 in these cells. Furthermore, we transfected miR-9, miR-34a, miR-181a, and miR-181c mimics into HepG2 cells and found that only miR-9 and miR-181a reduced the level of Gab2 proteins. miR-9 also reduced the Gab2 mRNA level, but miR-181a did not affect the Gab2 mRNA levels. Using a miRNA-Gab2 3′UTR binding reporter, we confirmed that miR-9 and miR-181a bind to the Gab2 3′UTR region. Finally, we introduced miR-9 and miR-181a mimics into HepG2 cells and found that cell proliferation and migration were significantly inhibited. In conclusion, we identified two novel miRNAs targeting Gab2 and provided potential drug targets for the prevention and treatment of liver cancer.

The role of anoctamin 1 in liver disease

“…miR‐9 can target the signalling integrin Gab2 to inhibit the proliferation and migration of HCC cells. 117 miR‐9 upregulation can inhibit ANO1 expression, 103 but whether miR‐9 further inhibits cell proliferation and migration in HCC through ANO1 still needs further investigation. Ferroptosis is a key cell death response triggered upon treatment of multiple tumours.…”

“…This finding suggested that diltiazem might play a role in the treatment of HCC, but further experimental studies are needed. miR‐9 can target the signalling integrin Gab2 to inhibit the proliferation and migration of HCC cells 117 . miR‐9 upregulation can inhibit ANO1 expression, 103 but whether miR‐9 further inhibits cell proliferation and migration in HCC through ANO1 still needs further investigation.…”