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MicroRNA-135a-3p is downregulated and serves as a tumour suppressor in ovarian cancer by targeting CCR2
Shufeng Duan1, Xuecai Dong1, Jing Hai1
1Department of Gynecology and Oncology, Xinxiang Central Hospital, Xinxiang, Henan, 453000, China.
Abstract:
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.
Insights
MicroRNA-135a-3p acts as a tumor suppressor in ovarian cancer. Its downregulation promotes cancer cell growth and metastasis by targeting C-C chemokine receptor type 2 (CCR2).
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- MicroRNAs (miRNAs) are key regulators in cancer development.
- miR-135a family members, including miR-135a-5p and miR-135a-3p, show tumor-suppressive roles in various cancers.
- The specific function and molecular mechanisms of miR-135a-3p in ovarian cancer remain unclear.
Purpose of the Study:
- To investigate the role of miR-135a-3p in ovarian carcinoma.
- To elucidate the molecular mechanisms by which miR-135a-3p affects ovarian cancer cell growth and metastasis.
Main Methods:
- Quantitative analysis of miR-135a-3p expression in ovarian cancer tissues.
- In vitro assays assessing the effects of miR-135a-3p overexpression on cell proliferation, migration, and invasion.
- Luciferase reporter assays to identify miR-135a-3p targets.
- In vivo studies using xenograft models.
Main Results:
- miR-135a-3p expression is significantly downregulated in ovarian carcinoma tissues.
- Overexpression of miR-135a-3p inhibits ovarian cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT).
- C-C chemokine receptor type 2 (CCR2) is identified as a direct target of miR-135a-3p.
- CCR2 depletion mimics miR-135a-3p's inhibitory effects, and CCR2 overexpression rescues these effects.
- miR-135a-3p suppresses tumor growth in vivo by targeting CCR2.
Conclusions:
- miR-135a-3p functions as a tumor suppressor gene in ovarian cancer.
- The tumor-suppressive role of miR-135a-3p is mediated through the regulation of CCR2.
- miR-135a-3p represents a potential therapeutic target for ovarian cancer treatment.
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