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长链非编码RNA癌症易感性候选基因9通过稳定缺氧诱导因子1α促进鼻咽癌发生。

The Long Noncoding RNA Cancer Susceptibility Candidate 9 Promotes Nasopharyngeal Carcinogenesis via Stabilizing HIF1α.

作者信息

Su Xiaoming, Li Guoli, Liu Weiwei

机构信息

Department of Otolaryngology, Cangzhou Central Hospital, Hebei Medical University , Cangzhou, China .

出版信息

DNA Cell Biol. 2017 May;36(5):394-400. doi: 10.1089/dna.2016.3615. Epub 2017 Feb 23.

Abstract

Increasing evidence has suggested that long noncoding RNAs (lncRNAs) play critical roles in cancer development. Nasopharyngeal carcinoma (NPC) is a disease with high incidence. Although remarkable progress has been made in understanding the molecular mechanism and therapy strategies in NPC, the potential involvement of lncRNAs in NPC remains largely unknown. In this study, we identified that lncRNA cancer susceptibility candidate 9 (CASC9) is highly expressed in NPC tissues, which facilitates cell growth and is correlated with a poor prognosis of cancer patients. The underlying molecular mechanism revealed that CASC9 interacts with HIF1α and enhances the stabilization of HIF1α. Activation of HIF1α by overexpressed CASC9 promotes the glycolysis and tumorigenesis of NPC cells. Downregulation of CASC9 significantly inhibits NPC cancer cell growth. Collectively, our results illustrated the oncogenic role of CASC9 in promoting the progression of NPC through regulating HIF1α, which imply that modulation of CASC9 expression may be a promising target in cancer therapy.

摘要

越来越多的证据表明,长链非编码RNA(lncRNA)在癌症发展中起着关键作用。鼻咽癌(NPC)是一种高发疾病。尽管在理解鼻咽癌的分子机制和治疗策略方面取得了显著进展,但lncRNA在鼻咽癌中的潜在作用仍 largely未知。在本研究中,我们发现lncRNA癌症易感性候选基因9(CASC9)在鼻咽癌组织中高表达,它促进细胞生长并与癌症患者的不良预后相关。潜在的分子机制表明,CASC9与HIF1α相互作用并增强HIF1α的稳定性。过表达的CASC9对HIF1α的激活促进了鼻咽癌细胞的糖酵解和肿瘤发生。CASC9的下调显著抑制鼻咽癌细胞的生长。总体而言,我们的结果说明了CASC9通过调节HIF1α在促进鼻咽癌进展中的致癌作用,这意味着调节CASC9的表达可能是癌症治疗中有前景的靶点。

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