MicroRNA-139 Suppresses Hepatocellular Carcinoma Cell Proliferation And Migration By Directly Targeting Topoisomerase ?

MicroRNAs(miRNAs)were reported to be associated with cancer progression and metastasis.MiRNA-139,which is located in 11q13.4 and has anti-oncogenic and anti-metastatic activity in humans,was identified to be downregulated in various malignant tumours.However,the main targets and signaling pathways that miR-139 controls in hepatocellular carcinoma(HCC)have not been fully elucidated.In this study,we explored the potential targets of tumour-suppressive miR-139 in HCC.Using combinational analysis of the data from four miRNA target prediction tools and biological experiments,we demonstrated that Topoisomerase I(TOP1)is a direct target of miR-139 in HCC.Previous studies showed that TOP1-induced DNA lesions exert a detrimental effect on cell survival,which made this enzyme a prime target for cancer therapies to kill fast-growing cancer cells.Several traditional topoisomerase inhibitors have showed good anticancer activity,but their side effects outnumbered their anticancer potential.Our study found that overexpression of miR-139 significantly inhibits HCC cell proliferation(P < 0.05)and migration(P < 0.05),which is largely due to TOP1 downregulation.The present work indicates that miR-139 exerts a tumour-suppressive effect during hepatocarcinogenesis via suppressing the expression of TOP1.Therefore,miR-139 has potential as a target for gene therapy applications in the treatment of HCC.