title: MiR-939 promotes the proliferation of human ovarian cancer cells by repressing APC2 expression.
abstract: Aberrant activation of the Wnt/β-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/β-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 3'-untranslated region (3'-UTR) of APC2 mRNA. Furthermore, we demonstrated that miR-939 could reduce the Wnt/β-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/β-catenin signal pathway through direct suppression of APC2 expression and might sever as a potential therapeutic target for ovarian cancer patients.
authors.affiliation: Department of Gynecology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, People's Republic of China. Electronic address: xiongyingguangzhou@163.com.
authors.forename: Xiong
authors.initials: X
authors.lastname: Ying
authors.affiliation: Department of Gynecology, The First People's Hospital of Yunnan Province, Kunming 650032, People's Republic of China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li-ya
authors.affiliation: Department of Medical Affairs, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, People's Republic of China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Department of Gynecology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, People's Republic of China.
authors.forename: Wang
authors.initials: W
authors.lastname: Yin
authors.affiliation: Department of Gynecology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, People's Republic of China.
authors.forename: Liu
authors.initials: L
authors.lastname: Ji-hong
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology*; D011485:Protein Binding / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; C115681:APC2 protein, human; D003598:Cytoskeletal Proteins; C000604729:MIRN939 microRNA, human; D035683:MicroRNAs
keywords: APC2; Cell proliferation; Human ovarian cancer; miR-939