MicroRNA-139 suppresses hepatocellular carcinoma cell proliferation and migration by directly targeting Topoisomerase I

MicroRNA-139通过直接靶向拓扑异构酶I抑制肝细胞癌细胞增殖和迁移

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Abstract

microRNAs (miRNAs) have been determined to be associated with cancer progression and metastasis. Mir-139 is located on 11q13.4 and exhibits anti-oncogenic and anti-metastatic activity in human cancers. It is downregulated in various malignant tumor types. In the present study, the potential functions and targets of miR-139 in hepatocellular carcinoma (HCC) were explored. Using a combinational analysis of four miRNA target prediction tools and biological experiments, it was determined that Topoisomerase I (TOP1) is a direct target of miR-139 in HCC. Several traditional topoisomerase inhibitors have demonstrated anticancer activity, but their side effects outnumbered their anticancer potential. The present study determined 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 study indicated that miR-139 exerts a tumor-suppressive effect during hepatocarcinogenesis via the suppression of expression of TOP1; therefore, miR-139 is a promising target for the treatment of HCC.

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