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.
Gynecol Oncol. 2014 Jul;134(1):129-37. doi: 10.1016/j.ygyno.2014.04.047. Epub 2014 Apr 30.
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.
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.
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.
The newly identified miR-31/ARID1A pathway provides insight into cervical cancer progression, and may represent a novel therapeutic target.
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。
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。
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。
新鉴定的 miR-31/ARID1A 通路为宫颈癌的进展提供了新的见解，可能代表了一种新的治疗靶点。
Zotero 插件