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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作者:Pengfei Zhang, Jikai Yin, Lijuan Yuan, Qing Wang, Xilin Du, Rui Dong, Chengguo Wang, Qiangshan Bai, Ling Ji, Guizhi Zhang, Jianguo Lu

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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