MicroRNA-301b-3p Contributes To Tumour Growth Of Human Hepatocellular Carcinoma By Repressing Vestigial Like Family Member 4

MicroRNAs(miRNAs) are key regulators in the tumour growth and metastasis of human hepatocellular carcinoma(HCC).Increasing evidence suggests that miR-301b-3p functions as a driver in various types of human cancer.However,the expression pattern of miR-301b-3p and its functional role as well as underlying molecular mechanism in HCC remain poorly known.Our study found that miR-301b-3p expression was significantly up-regulated in HCC tissues compared to adjacent non-tumour tissues.Clinical association analysis revealed that the high level of miR-301b-3p closely correlated with large tumour size and advanced tumour-node-metastasis stages.Importantly,the high miR-301b-3p level predicted a prominent poorer overall survival of HCC patients.Knockdown of miR-301b-3p suppressed cell proliferation,led to cell cycle arrest at G2/M phase and induced apoptosis of Huh7 and Hep3 B cells.Furthermore,miR-301b-3p knockdown suppressed tumour growth of HCC in mice.Mechanistically,miR-301b-3p directly bond to 3′UTR of vestigial like family member4(VGLL4)and negatively regulated its expression.The expression of VGLL4 mRNA was down-regulated and inversely correlated with miR-301b-3p level in HCC tissues.Notably,VGLL4 knockdown markedly repressed cell proliferation,resulted in G2/M phase arrest and promoted apoptosis of HCC cells.Accordingly,VGLL4 silencing rescued miR-301b-3p knockdown attenuated HCC cell proliferation,cell cycle progression and apoptosis resistance.Collectively,our results suggest that miR-301b-3p is highly expressed in HCC.miR-301b-3p facilitates cell proliferation,promotes cell cycle progression and inhibits apoptosis of HCC cells by repressing VGLL4.