Li Weiwei, Lin Ji, Huang Jianfen, Chen Zhuoying, Sheng Qunying, Yang Fang, Yang Xue, Cui Xiaojie
Department of Gynecology, Mindong Hospital Affiliated to Fujian Medical University, Fuan, Fujian 355000, P.R. China.
Department of Gynecology, Xiamen Fifth Hospital, Xiamen, Fujian 361101, P.R. China.
Oncol Lett. 2022 Jun 14;24(2):261. doi: 10.3892/ol.2022.13381. eCollection 2022 Aug.
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/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/M phase and apoptosis. Taken together, these results suggest that miR-409-5p acts as a tumor suppressor in OC by modulating DLGAP5 expression.
据报道，微小RNA（miRNA/miR）-409-5p与前列腺癌和乳腺癌有关；然而，其在卵巢癌（OC）中的功能作用仍不清楚。因此，本研究的目的是探讨miR-409-5p在OC中的临床意义和生物学功能。在此，进行逆转录定量PCR分析以检测OC组织和细胞系中miR-409-5p的表达。使用Fisher精确检验评估miR-409-5p表达与OC患者临床病理特征之间的关联。此外，进行细胞计数试剂盒-8检测以评估细胞增殖。通过流式细胞术分析评估细胞周期分布和凋亡，并通过双荧光素酶报告基因检测验证miR-409-5p的靶基因。结果表明，与相邻正常组织和上皮细胞相比，miR-409-5p在OC组织和细胞系中的表达分别显著下调。此外，低miR-409-5p表达与肿瘤大小（P = 0.044）和国际妇产科联合会分期系统（P = 0.005）显著相关。值得注意的是，miR-409-5p的过表达抑制细胞增殖，并诱导OC细胞的G/M期阻滞和凋亡。机制上，盘状大蛋白相关蛋白5（DLGAP5）被鉴定为miR-409-5p的新靶标，其受到miR-409-5p的负调控。与相邻正常组织和上皮细胞相比，DLGAP5在OC组织和细胞系中的表达分别显著上调。此外，DLGAP5的过表达逆转了miR-409-5p对SKOV-3细胞增殖、G/M期和凋亡的影响。综上所述，这些结果表明miR-409-5p通过调节DLGAP5表达在OC中发挥肿瘤抑制作用。
