MicroRNA-135a-3p is downregulated and serves as a tumour suppressor in ovarian cancer by targeting CCR2

被引:37
作者
Duan, Shufeng [1 ]
Dong, Xuecai [1 ]
Hai, Jing [1 ]
Jiang, Jinghong [2 ]
Wang, Wenxiang [1 ]
Yang, Jing [1 ]
Zhang, Wei [2 ]
Chen, Caixia [1 ]
机构
[1] Xinxiang Cent Hosp, Dept Gynecol & Oncol, 56 Jin Sui Da St, Xinxiang 453000, Henan, Peoples R China
[2] Wuhan Univ, Zhongnan Hosp, Obstet & Gynecol Dept, Wuhan 430070, Hubei, Peoples R China
关键词
Ovarian cancer; miR-135a-3p; CCR2; Migration; Invasion; CELL-PROLIFERATION; PANCREATIC-CANCER; CERVICAL-CANCER; LUNG-CANCER; CHEMOKINES; GROWTH; AXIS; MIR-135A-5P; SENSITIVITY; METASTASIS;
D O I
10.1016/j.biopha.2018.08.044
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
MicroRNAs have been demonstrated to play a crucial role in the development of ovarian cancer. Many studies prove that forms of miR-135a, including miR-135a-5p and miR-135a-3p, serve as tumour suppressors in multiple cancers. Nevertheless, the precise function of miR-135a-3p and the molecular mechanisms underlying the involvement of miR-135a-3p in ovarian carcinoma cell growth and metastasis remain largely unknown. Herein, we report that miR-135a-3p expression was significantly downregulated in ovarian carcinoma tissues compared with corresponding adjacent non-tumour tissues. Ectopic miR-135a-3p expression inhibited ovarian carcinoma cell proliferation, migration and invasion in vitro. Additionally, the overexpression of miR-135a-3p inhibited epithelial-mesenchymal transition (EMT) in ovarian cancer cells. A luciferase reporter assay confirmed that the C-C chemokine receptor type 2 (CCR2) gene was the target of miR-135a-3p. In addition, CCR2 depletion mimicked the inhibitory effects of miR-135a-3p on ovarian cancer cells in vitro. Rescue experiments using CCR2 overexpression further verified that CCR2 was a functional target of miR-135a-3p. Xenograft model assays demonstrated that miR-135a-3p functions as an anti-oncogene by targeting CCR2 in vivo. Taken together, these data prove that miR-135a-3p serves as a tumour suppressor gene in ovarian cancer by regulating CCR2.
引用
收藏
页码:712 / 720
页数:9
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