MiR-31 is an independent prognostic factor and functions as an oncomir in cervical cancer via targeting ARID1A
MiR-31 is an independent prognostic factor and functions as an oncomir in cervical cancer via targeting ARID1A
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Y MiR-31 是一个独立的预后因素，通过靶向 ARID1A 作为宫颈癌的癌基因
DOI：
10.1016/j.ygyno.2014.04.047
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发表时间：
2014-07-01
影响因子：
4.7
通讯作者：
Li, Hui
中科院分区：
文献类型：
--
作者：
Wang, Nan;Zhou, Yun;Li, Hui
目标。MicroRNAs（miRNAs）在肿瘤的发生发展中起着重要的作用。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。采用定量RT-PCR检测miR-31在宫颈癌细胞系和患者标本中的表达。进一步分析miR-31上调的临床病理意义。进行MU、菌落形成、细胞凋亡、细胞周期、创面愈合和Transwell侵袭试验，并建立异种移植物模型。荧光素酶报告基因实验证实了miR-31的靶基因，并在细胞系和患者标本中验证了结果。MiR-31在宫颈癌细胞系和临床组织中显著上调。高水平的miR-31与较高的FIGO分期、淋巴结转移、血管受累和深部间质浸润显著相关。miR-31高表达患者的总生存率低于低表达患者。多因素Cox回归分析显示，MiR-31是宫颈癌的独立预后因素。在体外，miR-31的下调会损害细胞增殖、集落形成、细胞迁移和侵袭，并抑制异种移植物肿瘤的生长。ARID1A被证实是miR-31的直接靶点，在患者标本中miR-31和ARID1A的逆表达进一步证实了这一点。新发现的miR-31/ARID1A通路提供了对宫颈癌进展的深入了解，并可能代表一种新的治疗靶点。(C) 2014爱思唯尔公司版权所有。
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.