MicroRNA‐216b suppresses the cell growth of hepatocellular carcinoma by inhibiting Ubiquitin‐specific peptidase 28 expression

Abstract

Abstract MicroRNA‐216b (miR‐216b) has been reported to be downregulated in several tumors, its mechanism is still little‐studied in hepatocellular carcinoma (HCC). In the present study, we found that miR‐216b was downregulated in HCC, but Ubiquitin‐specific peptidase 28 (USP28) was upregulated. In addition, Kaplan‐Meier‐plotter analysis indicated that liver cancer patients with high miR‐216b expression had a longer overall survival, but patients with high USP28 had a shorter overall survival. Further studies showed that overexpression of miR‐216b inhibited HCC cell growth, and molecular investigations revealed that miR‐216b targeted USP28 and inhibited its expression in HCC cells. In addition, overexpression of miR‐216b suppressed the substrates' expression of USP28, for example, c‐Myc, and miR‐216b overexpression also inhibited Cyclin E expression as well as upregulating p27 expression, both of which were the downstream signals of c‐Myc. These results indicated that miR‐216b downregulated USP28/c‐Myc signaling in HCC cells. Collectively, this study demonstrated that miR‐216b/c‐Myc axis could be as a potential target for HCC therapy in the future.

Keywords

• cell growth
• c‐Myc
• hepatocellular carcinoma
• MicroRNA‐216b
• USP28