MicroRNA-34a suppresses aggressiveness of hepatocellular carcinoma by modulating , and Caspase-3.

Accumulating evidence suggests an antineoplastic role of () in human cancer. However, its precise biological functions stay largely elusive. Our study was aimed to investigate the impact of on hepatocellular carcinoma (HCC) and its underlying apoptosis related mechanisms in vitro, as well as the association of ,  and  expression with patient survival of HCC using publicly accessed datasets. The HBV-expressing Hep3B and SNU-449 cell lines with or without enforced expression of were in vitro cultured for cell proliferation, colony formation, wound healing, cell invasion, and 3D spheroid formation. Quantitative reverse transcription PCR (RT-qPCR) was performed for  expression. Caspase-3 (CASP3) activity was determined using a CaspACE Assay System. Kaplan-Meier survival curves were used to analyze the associations of miR-34a,  and  expression and overall survival in HCC. Meta-analysis was performed to examine the differential expression of  and  between primary HCC vs normal tissues.  The results in vitro showed that enforced expression significantly inhibited cell proliferation, migration, and invasion of both Hep3B and SNU-449. RT-qPCR results demonstrated that miR-34a could significantly suppress  and  expression, particularly in SNU-449. CASP3 activity in both Hep3B and SNU-449 increased in treatment group. Overexpressed  and  were observed in primary HCC vs normal tissues. Survival analyses showed that HCC patients with either high , or low , or low  expression had better survival than their opposite counterparts, respectively. : Our study suggested that can modulate the expression of , and CASP3 activity, thereby repressing tumor aggressiveness and expediting apoptosis in liver cancer cells.