MicroRNA-409-5p inhibits cell proliferation, and induces G2/M phase arrest and apoptosis by targeting DLGAP5 in ovarian cancer cells

摘要

MicroRNA (miRNA/miR)-409-5p has been reported to be implicated in prostate and breast cancers; however, its functional role in ovarian cancer (OC) remains unclear. Therefore the aim of the present study was to investigate the clinical significance and biological function of miR-409-5p in OC. Here, reverse transcription-quantitative PCR analysis was performed to detect miR-409-5p expression in OC tissues and cell lines. The association between miR-409-5p expression and the clinicopathological characteristics of patients with OC was assessed using the Fisher's exact test. Furthermore, the Cell Counting Kit-8 assay was performed to assess cell proliferation. Cell cycle distribution and apoptosis were evaluated via flow cytometric analysis, and the target gene of miR-409-5p was validated via the dual-luciferase reporter assay. The results demonstrated that miR-409-5p expression was significantly downregulated in OC tissues and cell lines compared with adjacent normal tissues and epithelial cells, respectively. In addition, low miR-409-5p expression was significantly associated with tumor size (P=0.044) and the International Federation of Gynecology and Obstetrics staging system (P=0.005). Notably, overexpression of miR-409-5p suppressed cell proliferation, and induced G(2)/M phase arrest and apoptosis of OC cells. Mechanistically, discs large-associated protein 5 (DLGAP5) was identified as a novel target of miR-409-5p, which was negatively regulated by miR-409-5p. DLGAP5 expression was significantly upregulated in OC tissues and cell lines compared with adjacent normal tissues and epithelial cells, respectively. Furthermore, overexpression of DLGAP5 reversed the effects of miR-409-5p on SKOV-3 cell proliferation, and G(2)/M phase and apoptosis. Taken together, these results suggest that miR-409-5p acts as a tumor suppressor in OC by modulating DLGAP5 expression.

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