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

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.