Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China.
Life Sci. 2018 Oct 1;210:263-270. doi: 10.1016/j.lfs.2018.08.043. Epub 2018 Aug 20.
Survival of ovarian cancer patients is generally poor, partly because most of them are already at an advanced stage when diagnosed. The purpose of this study was to screen prognostic miRNAs for ovarian cancer, and to explore the underlying mechanisms.
Integrated meta-analysis of miRNA microarrays retrieved from public repositories was employed to identify clinically significant miRNAs involved in ovarian cancer. Targets of candidate miRNA were predicted using four online databases, and validated with dual luciferase assay. Loss and gain of function were performed to investigate the role of miR27a in the growth of ovarian cancer cell lines.
Based on cross-validation results in multiple datasets, we recognized hsa-miR-27a as an oncogenic molecular and a prognostic factor for ovarian cancer patients. Dual luciferase assay indicated tumor suppressor FOXO1 was a direct target of miR-27a. In addition, hsa-miR-27a could stimulate SKOV3 and A2780 cell proliferation and migration by regulating the expression of FOXO1.
In summary, our results indicate that miR-27a can promote progression of ovarian cancer by mediating FOXO1. To our knowledge, this is the first study focusing on the role of miR-27a/FOXO1 axis using the microarray meta-analysis in ovarian cancer. Furthermore, inhibiting miR-27a expression may be a new strategy for the treatment of ovarian cancer.
卵巢癌患者的生存率普遍较差，部分原因是大多数患者在确诊时已经处于晚期。本研究旨在筛选与卵巢癌相关的预后 miRNA，并探讨其潜在机制。
综合分析公共数据库中 miRNA 微阵列的元分析，以确定与卵巢癌相关的临床有意义的 miRNA。使用四个在线数据库预测候选 miRNA 的靶标，并通过双荧光素酶报告基因实验进行验证。通过失活和功能获得实验来研究 miR27a 在卵巢癌细胞系生长中的作用。
基于多个数据集的交叉验证结果，我们将 hsa-miR-27a 识别为致癌分子和卵巢癌患者的预后因素。双荧光素酶报告基因实验表明，肿瘤抑制因子 FOXO1 是 miR-27a 的直接靶标。此外，hsa-miR-27a 可以通过调节 FOXO1 的表达来刺激 SKOV3 和 A2780 细胞的增殖和迁移。
综上所述，我们的研究结果表明，miR-27a 通过介导 FOXO1 促进卵巢癌的进展。据我们所知，这是第一项使用卵巢癌微阵列元分析研究 miR-27a/FOXO1 轴作用的研究。此外，抑制 miR-27a 的表达可能是治疗卵巢癌的一种新策略。
