MiR-3196, a p53-responsive microRNA, functions as a tumor suppressor in hepatocellular carcinoma by targeting FOXP4

Increasing evidences demonstrate that miRNAs play an important role in development and progression of hepatocellular carcinoma (HCC). Recent studies indicate that miR-3196 regulates tumorigenesis in breast and lung cancer. However, its role and regulatory mechanism remains unknown in hepatocellular carcinoma. Here, we found that miR-3196 was downregulated in HCC tissues and decreased miR-3196 was correlated with tumor size (P=0.0297) and TNM stage (P=0.034). Forced miR-3196 suppressed HCC cell growth and chemoresistance in vivo and in vitro. Further mechanistic studies revealed that the tumor suppressor p53 transcriptionally upregulated miR-3196 expression by binding to its promoter region in HCC cells. Additional, we also found that FOXP4 was a downstream target of miR-3196 and increased miR-3196 inhibited FOXP4 expression which led to HCC growth suppression and cell apoptosis increase. Collectively, our data shed a new role of miR-3196 in HCC and indicates that p53-dependent, miR-3196-medicated FOXP4 pathway inhibits the tumorigenesis of HCC.