miR-532-5p 是一种预后标志物，通过靶向 TWIST1 抑制上皮性卵巢癌细胞的增殖和侵袭。
miR-532-5p is a prognostic marker and suppresses cells proliferation and invasion by targeting TWIST1 in epithelial ovarian cancer.
机构信息
Department of Obstetrics and Gynecology, Linyi People's Hospital, Linyi, Shandong, China.
出版信息
Eur Rev Med Pharmacol Sci. 2018 Sep;22(18):5842-5850. doi: 10.26355/eurrev_201809_15911.
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.
目的
miR-532-5p 在卵巢上皮性癌（EOC）中存在失调。然而，其潜在的生物学功能和临床意义尚未得到充分解释。本研究旨在探讨 miR-532-5p 在 EOC 中的预后价值和潜在作用。
患者和方法
采用实时定量 PCR 检测 miR-532-5p 和 TWIST1 同源物 1（TWIST1）mRNA 的表达。统计分析 miR-532-5p 表达与临床病理因素的相关性。通过 Kaplan-Meier 分析和 Cox 比例风险回归模型揭示 miR-532-5p 表达与患者生存的相关性。通过细胞计数试剂盒-8、集落形成和 Transwell 侵袭实验分别评估 miR-532-5p 对细胞增殖和侵袭的影响。通过荧光素酶活性、RT-PCR 和 Western blot 实验证实 miR-532-5p 的靶基因。
结果
我们发现 miR-532-5p 在 EOC 组织和细胞系中显著下调，其表达水平与分级（p=0.011）、FIGO 分期（p=0.004）和远处转移（p=0.008）高度相关。此外，miR-532-5p 高表达患者的总生存时间明显长于 miR-532-5p 低表达患者（p=0.0058）。多变量回归分析确定 miR-532-5p 下调是 EOC 患者独立的不良预后因素。功能分析表明，miR-532-5p 过表达抑制 EOC 细胞的增殖、集落形成和侵袭。机制研究证实 TWIST1 是 miR-532-5p 的直接靶基因。进一步的体外实验表明，TWIST1 的恢复表达减弱了 miR-532-5p 对肿瘤进展的抑制作用。
结论
我们的数据表明，miR-532-5p 不仅可以作为一种新的预后标志物，而且可以作为 EOC 分子治疗的潜在靶点。
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