MiR-642 serves as a tumor suppressor in hepatocellular carcinoma by regulating SEMA4C and p38 MAPK signaling pathway.

Abstract

Hepatocellular carcinoma (HCC) is a malignant tumor with high incidence and high risk. Study of the role and mechanism of miRNAs are a hot spot of research providing new treatment ideas in malignant tumors. The effect of miR-642a on HCC progression and the underlying molecular mechanism were investigated. Expression of miR-642a and SEMA4C was measured by western blot analysis and RT-PCR. miR-642a expression was elevated while SEMA4C expression was attenuated in HCC tissues and cells. Results of luciferase reporter and western blot analyses show that miR-642a modulated SEMA4C expression by binding to its 3′UTR. Moreover, miR-642a negatively regulated SEMA4C expression. HCC cell migration and invasion was tested by Transwell assays. The findings revealed that the number of migrated and invaded cells were reduced by miR-642a mimic and raised by miR-642a inhibitor, indicating that miR-642a showed a suppression effect on HCC cell migration and invasion. Additionally, the migration and invasion of HCC cells were inhibited by SEMA4C siRNA, and SEMA4C reversed miR-642a effect on HCC migration and invasion. Furthermore, p38 MAPK signaling pathway was proven to be inhibited by miR-642a mimic, whereas facilitated by miR-642a inhibitor and SEMA4C siRNA could overturn the promotion effect of miR-642a inhibitor. Briefly, miR-642a targeted SEMA4C to repress HCC cell migration and invasion through p38 MAPK signaling pathway providing a new strategy for treatment of HCC patients.