MicroRNA-939 induces apoptosis in human liver cancer cells by targeting CRKL expression.

INTRODUCTION

Over the years, microRNAs (miRs) have been shown to exhibit therapeutic implications in the treatment of cancer. Consistently, this study was designed to examine the expression profile and to decipher the therapeutic implications of miR-939 in human liver cancer.

MATERIAL AND METHODS

Expression profiling was performed by qRT-PCR and the proliferation rate of liver cancer cells was monitored by Cell Counting Kit 8 (CCK8) and clonogenic assays. 4',6-diamidino-2-phenylindole (DAPI) staining and annexin V-FITC assays were used to determine the induction of apoptosis. Ultrastructural analysis was performed by transmission electron microscopy (TEM). Western blotting was used to determine protein expression.

RESULTS

miR-939 was found to be significantly ( < 0.05) downregulated in the liver cancerous tissues and cell lines. miR-939 overexpression significantly ( < 0.05) decreased the proliferation and colony formation of liver cancer cells. Ultrastructural analysis, DAPI and annexin V/PI assays showed induction of apoptosis in miR-939 overexpressing liver cancer cells. This was accompanied by upregulation of Bax, p53 and suppression of Bcl-2. analysis showed CRKL to be the target of miR-939. The downregulation of CRKL mimicked the molecular effects of miR-939 in liver cancer cells. Nonetheless, CRKL overexpression abolished the growth inhibitory effects of miR-939 on liver cancer cells.

CONCLUSIONS

The present study established the role of the miR-939/CRKL molecular axis in regulation of liver cancer proliferation, and it may also prove an essential therapeutic target for its management.