miR-31 是宫颈癌的一个独立预后因子，通过靶向 ARID1A 发挥致癌作用。

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

机构信息

Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, China.

Wu Han Tumor Hospital, China.

出版信息

Gynecol Oncol. 2014 Jul;134(1):129-37. doi: 10.1016/j.ygyno.2014.04.047. Epub 2014 Apr 30.

DOI:10.1016/j.ygyno.2014.04.047

PMID:24793973

Abstract

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 MTT, 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.

摘要

目的

微小 RNA（miRNA）在肿瘤的发生和发展中起着重要作用。本研究旨在探讨 miR-31 在宫颈癌中的作用，并阐明 miR-31 对 ARID1A 的调控作用。

方法

采用定量 RT-PCR 检测宫颈癌细胞系和患者标本中 miR-31 的表达。进一步分析 miR-31 上调的临床病理意义。进行 MTT、集落形成、凋亡、细胞周期、划痕愈合和 Transwell 侵袭实验，以及异种移植模型。采用荧光素酶报告基因检测证实 miR-31 的靶基因，并在细胞系和患者标本中验证结果。

结果

miR-31 在宫颈癌细胞系和临床组织中明显上调。高水平的 miR-31 与 FIGO 分期较高、淋巴结转移、血管浸润和深层基质浸润显著相关。miR-31 高表达的患者总生存时间明显低于 miR-31 低表达的患者。多因素 Cox 回归分析显示，miR-31 是宫颈癌的独立预后因素。下调 miR-31 可显著抑制体外细胞增殖、集落形成、细胞迁移和侵袭，并抑制体内异种移植肿瘤生长。ARID1A 被验证为 miR-31 的直接靶基因，这在患者标本中进一步证实了 miR-31 和 ARID1A 的反式表达。