H Wei1, Q-L Tang, K Zhang, J-J Sun, R-F Ding. 1. Department of Obstetrics and Gynecology, Linyi People's Hospital, Linyi, Shandong, China. drf13310@163.com.
Abstract
OBJECTIVE: Dysregulated miR-532-5p has been observed in epithelial ovarian cancer (EOC). However, the potential biological function and clinical significance have not been fully explained. The study aimed to investigate the prognostic value and potential role of miR-532-5p in EOC. PATIENTS AND METHODS: MiR-532-5p and Twist homolog 1 (TWIST1) mRNA expression were examined using quantitative real-time PCR. The correlation of miR‑532-5p expression with clinicopathological factors was statistically analyzed. Kaplan-Meier analysis and Cox proportional hazards regression models were explored to reveal the correlations of miR-532-5p expression with survival of patients. Cell Counting Kit-8, colony formation and transwell invasion assays were performed to evaluate the effects of miR-532-5p on cell proliferation and invasion, respectively. MiR‑532-5p target genes were confirmed using luciferase activity, RT-PCR and Western blot assays. RESULTS: We found that miR-532-5p was significantly decreased in EOC tissue and cell lines, and its expression levels were highly correlated with grade (p = 0.011), FIGO stage (p = 0.004) and distant metastasis (p = 0.008). In addition, overall patient survival for those with high miR-532-5p expression was significantly longer than those patients with low miR-532-5p expression (p = 0.0058). Multivariate regression analysis identified miR-532-5p down-regulation as an independent unfavorable prognostic factor in EOC patients. Function assays showed that overexpression of miR-532-5p inhibited proliferation, colony formation and invasion of EOC cells. Mechanistic investigations confirmed TWIST1 as a direct target of miR-532-5p. Further in vitro assay indicated that restored expression of TWIST1 dampened miR-532-5p-mediated suppression of tumor progression. CONCLUSIONS: Our data suggested that miR-532-5p may act not only as a novel prognostic marker, but also as a potential target for molecular therapy of EOC.
OBJECTIVE: Dysregulated miR-532-5p has been observed in epithelial ovarian cancer (EOC). However, the potential biological function and clinical significance have not been fully explained. The study aimed to investigate the prognostic value and potential role of miR-532-5p in EOC. PATIENTS AND METHODS: MiR-532-5p and Twist homolog 1 (TWIST1) mRNA expression were examined using quantitative real-time PCR. The correlation of miR‑532-5p expression with clinicopathological factors was statistically analyzed. Kaplan-Meier analysis and Cox proportional hazards regression models were explored to reveal the correlations of miR-532-5p expression with survival of patients. Cell Counting Kit-8, colony formation and transwell invasion assays were performed to evaluate the effects of miR-532-5p on cell proliferation and invasion, respectively. MiR‑532-5p target genes were confirmed using luciferase activity, RT-PCR and Western blot assays. RESULTS: We found that miR-532-5p was significantly decreased in EOC tissue and cell lines, and its expression levels were highly correlated with grade (p = 0.011), FIGO stage (p = 0.004) and distant metastasis (p = 0.008). In addition, overall patient survival for those with high miR-532-5p expression was significantly longer than those patients with low miR-532-5p expression (p = 0.0058). Multivariate regression analysis identified miR-532-5p down-regulation as an independent unfavorable prognostic factor in EOC patients. Function assays showed that overexpression of miR-532-5p inhibited proliferation, colony formation and invasion of EOC cells. Mechanistic investigations confirmed TWIST1 as a direct target of miR-532-5p. Further in vitro assay indicated that restored expression of TWIST1 dampened miR-532-5p-mediated suppression of tumor progression. CONCLUSIONS: Our data suggested that miR-532-5p may act not only as a novel prognostic marker, but also as a potential target for molecular therapy of EOC.
Authors: Vu Hong Loan Nguyen; Chenyang Yue; Kevin Y Du; Mohamed Salem; Jacob O'Brien; Chun Peng Journal: Int J Mol Sci Date: 2020-09-25 Impact factor: 5.923