MiR-939 promotes the proliferation of human ovarian cancer cells by repressing APC2 expression

摘要

Aberrant activation of the Wnt/beta-catenin signal pathway is frequently observed in various human cancers. Therefore, it was speculated that adenomatous polyposis coli 2 (APC2) could play important roles in activating the Wnt/b-catenin pathway. In this present study, miR-939 expression was markedly upregulated in ovarian cancer tissues and ovarian cancer cells. In functional assays, Overexpression of miR-939 promoted the proliferation and anchorage-independent growth of ovarian cancer cells, whereas inhibition of miR-939 inhibited this effect. Bioinformatics analysis further revealed APC2, a putative tumor suppressor as a potential target of miR-939. Result of luciferase reporter assays showed that miR-939 directly binds to the 30-untranslated region (30-UTR) of APC2 mRNA. Furthermore, we demonstrated that miR-939 could reduce the Wnt/b-catenin signal pathway by suppressing APC2 directly, resulting in increasing expression of CyclinD1, MYC and TCF. In functional assays, APC2-silenced in miR-939-in-transfected ES-2 cells have positive effect to promote cell proliferation, suggesting that direct APC2 downregulation is required for miR-939-induced ovarian cancer cell proliferation. In sum, our data provided compelling evidence that miR-939 functioned as a potential tumor promoter by regulating the Wnt/b-catenin signal pathway through direct suppression of APC2 expression and might sever as a potential therapeutic target for ovarian cancer patients. (C) 2015 Elsevier Masson SAS. All rights reserved.