MiR-31 is an independent prognostic factor and functions as an oncomir in cervical cancer via targeting ARID1A

被引:73
作者
Wang, Nan [1 ]
Zhou, Yun [2 ]
Zheng, Lijuan [1 ]
Li, Hui [1 ]
机构
[1] Huazhong Univ Sci & Technol, Ctr Human Genome Res, Key Lab Mol Biophys, Minist Educ,Coll Life Sci & Technol,Cardio X Inst, Wuhan 430074, Peoples R China
[2] Wu Han Tumor Hosp, Wuhan, Peoples R China
关键词
miR-31; Cervical cancer; ARID1A; Cell metastasis; Cell proliferation; EXPRESSION PROFILES; MICRORNA EXPRESSION; TUMOR PROGRESSION; MUTATIONS; ANGIOGENESIS; SUPPRESSOR; MIGRATION; INVASION; RNAS;
D O I
10.1016/j.ygyno.2014.04.047
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Objectives. MicroRNAs(miRNAs) play important roles in tumor development and progression. The purposes of this study were to investigate the role of miR-31 in cervical cancer and clarified the regulation of ARID1A by miR-31. Methods. Quantitative RT-PCR was used to examine miR-31 expression in cervical cancer cell lines and patient specimens. The clinicopathological significance of miR-31 upregulation was further analyzed. The MU, colony formation, apoptosis, cell cycle, wound healing and Transwell invasion assays, and a xenograft model were performed. A luciferase reporter assay was conducted to confirm the target gene of miR-31, and the results were validated in cell lines and patient specimens. Results. MiR-31 was significantly up-regulated in cervical cancer cell lines and clinical tissues. The high miR-31 level was significantly correlated with higher FIGO stage, node metastasis, vascular involvement and deep stromal invasion. Patients with high expression of miR-31 had poorer overall survival than patients with low expression. MiR-31 was an independent prognostic factor in cervical cancer in multivariate Cox regression analysis. Down-regulation of miR-31 impaired cell proliferation, colony formation, and cell migration and invasion in vitro, and inhibited xenograft tumor growth in vivo. ARID1A was verified as a direct target of miR-31, which was further confirmed by the inverse expression of miR-31 and ARID1A in patient specimens. Conclusions. The newly identified miR-31/ARID1A pathway provides insight into cervical cancer progression, and may represent a novel therapeutic target. (C) 2014 Elsevier Inc. All rights reserved.
引用
收藏
页码:129 / 137
页数:9
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