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

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机构: [1]Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Dept Gynecol, Guangzhou 510060, Guangdong, Peoples R China [2]First Peoples Hosp Yunnan Prov, Dept Gynecol, Kunming 650032, Peoples R China [3]Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Dept Med Affairs, Guangzhou 510060, Guangdong, Peoples R China
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关键词: miR-939 Human ovarian cancer APC2 Cell proliferation

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.

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出版当年[2015]版:
大类 | 4 区 医学
小类 | 4 区 医学:研究与实验 4 区 药学
最新[2023]版:
大类 | 2 区 医学
小类 | 1 区 药学 2 区 医学:研究与实验
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出版当年[2014]版:
Q3 PHARMACOLOGY & PHARMACY Q3 MEDICINE, RESEARCH & EXPERIMENTAL
最新[2023]版:
Q1 MEDICINE, RESEARCH & EXPERIMENTAL Q1 PHARMACOLOGY & PHARMACY

影响因子: 最新[2023版] 最新五年平均 出版当年[2014版] 出版当年五年平均 出版前一年[2013版] 出版后一年[2015版]

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第一作者机构: [1]Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Dept Gynecol, Guangzhou 510060, Guangdong, Peoples R China [*1]Department of Gynecology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, No. 651, Dongfengdong Road, Guangzhou 510060, People’s Republic of China
通讯作者:
通讯机构: [1]Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Dept Gynecol, Guangzhou 510060, Guangdong, Peoples R China [*1]Department of Gynecology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, No. 651, Dongfengdong Road, Guangzhou 510060, People’s Republic of China
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