MicroRNA-135a-3p is downregulated and serves as a tumour suppressor in ovarian cancer by targeting CCR2
| Autor: | Wenxiang Wang, Jinghong Jiang, Wei Zhang, Shufeng Duan, Caixia Chen, Jing Yang, Xuecai Dong, Jing Hai |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
CCR2 Receptors CCR2 Down-Regulation Mice Nude Biology Metastasis 03 medical and health sciences Chemokine receptor 0302 clinical medicine In vivo Cell Movement Ovarian carcinoma Cell Line Tumor microRNA medicine Animals Humans Genes Tumor Suppressor Neoplasm Invasiveness Neoplasm Metastasis Cell Proliferation Pharmacology Ovarian Neoplasms Mice Inbred BALB C Base Sequence Cell growth General Medicine medicine.disease Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology Phenotype 030220 oncology & carcinogenesis Gene Knockdown Techniques Cancer research Female Ovarian cancer |
| Zdroj: | Biomedicinepharmacotherapy = Biomedecinepharmacotherapie. 107 |
| ISSN: | 1950-6007 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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