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HuR调控的lncRNA NEAT1在卵巢癌发生发展中的稳定性

HuR-regulated lncRNA NEAT1 stability in tumorigenesis and progression of ovarian cancer.

作者信息

Chai Yiqing, Liu Jie, Zhang Zhikun, Liu Liwei

机构信息

The Ultrasound Centre, Tianjin central hospital of gynecology obstetrics, Tianjin, 300052, China.

The Department of Urology, The Second hospital of Tianjin medical university, Tianjin, 300211, China.

出版信息

Cancer Med. 2016 Jul;5(7):1588-98. doi: 10.1002/cam4.710. Epub 2016 Apr 14.

Abstract

Long noncoding RNAs (lncRNAs) have recently emerged as pivotal regulators in governing fundamental biological processes, as well as in tumorigenesis. The nuclear paraspeckle assembly transcript 1 (NEAT1) is one of the most highly regulated lncRNAs in recent genomic datasets, however, its biological role and regulatory mechanism in ovarian cancer (OC) development and progression are poorly defined. In this study, we identified that NEAT1 was up-regulated in OC patients and cell lines, and its expression was associated with the FIGO stage and lymph node metastasis. Furthermore, the ectopic expression of NEAT1_1 in OVCAR-3 cell lines promoted cell proliferation and invasion, whereas knockdown of NEAT1_1 did the opposite. Furthermore, NEAT1_1 was stabilized by an RNA-binding protein HuR, but suppressed by miR-124-3p in OC cells. Accordingly, the increased HuR mRNA and decreased miR-124-3p levels were observed in OC patients. These results suggested that lncRNA NEAT1, whose expression was collaboratively controlled by HuR and miR-124-3p, could regulate ovarian carcinogenesis and may serve as a potential target for antineoplastic therapies.

摘要

长链非编码RNA(lncRNAs)最近已成为调控基本生物学过程以及肿瘤发生的关键调节因子。核旁斑组装转录本1(NEAT1)是近期基因组数据集中调控最为严格的lncRNAs之一,然而,其在卵巢癌(OC)发生发展中的生物学作用和调控机制仍不清楚。在本研究中,我们发现NEAT1在OC患者和细胞系中上调,其表达与国际妇产科联盟(FIGO)分期和淋巴结转移相关。此外,NEAT1_1在OVCAR-3细胞系中的异位表达促进了细胞增殖和侵袭,而敲低NEAT1_1则产生相反的效果。此外,NEAT1_1在OC细胞中被RNA结合蛋白HuR稳定,但被miR-124-3p抑制。因此,在OC患者中观察到HuR mRNA水平升高和miR-124-3p水平降低。这些结果表明,lncRNA NEAT1的表达受HuR和miR-124-3p共同控制,可调节卵巢癌发生,可能作为抗肿瘤治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e749/4944886/7826500aee94/CAM4-5-1588-g001.jpg

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