长链非编码RNA NEAT1通过miR-34a/c-Met轴增强肾细胞癌的上皮-间质转化和化疗耐药性。

The long non-coding RNA NEAT1 enhances epithelial-to-mesenchymal transition and chemoresistance via the miR-34a/c-Met axis in renal cell carcinoma.

作者信息

Liu Fei, Chen Na, Gong Yanchun, Xiao Ruihai, Wang Weichao, Pan Zhengyue

机构信息

Department of Urology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.

Department of Breast Surgery, The Fourth Affiliated Hospital of Nanchang University, Nanchang 330003, China.

出版信息

Oncotarget. 2017 May 10;8(38):62927-62938. doi: 10.18632/oncotarget.17757. eCollection 2017 Sep 8.

Abstract

Long non-coding RNAs (lncRNAs) have emerged as new gene regulators and prognostic markers in various cancers. Although the lncRNA nuclear enriched abundant transcript 1 (NEAT1) has been associated with tumorigenesis, its functions in renal cell carcinoma (RCC) have not been elucidated. We determined that NEAT1 is up-regulated in RCC tissue compared to corresponding non-tumor tissue. High NEAT1 expression was associated with tumor progression and poor survival in RCC patients. NEAT1 knockdown suppressed RCC cell proliferation by inhibiting cell cycle progression, and inhibited RCC cell migration and invasion by reversing the epithelial-to-mesenchymal transition phenotype. Down-regulation of NEAT1 increased the sensitivity of RCC cells to sorafenib . Mechanistic analysis revealed that NEAT1 acts as a competitive sponge for miR-34a, which prevents inhibition of c-Met. Thus, NEAT1 promotes RCC progression through the miR-34a/c-Met axis.

摘要

长链非编码RNA(lncRNAs)已成为各种癌症中新的基因调节因子和预后标志物。尽管长链非编码RNA核富集丰富转录本1(NEAT1)与肿瘤发生有关,但其在肾细胞癌(RCC)中的功能尚未阐明。我们确定,与相应的非肿瘤组织相比,NEAT1在RCC组织中上调。NEAT1高表达与RCC患者的肿瘤进展和不良生存相关。NEAT1敲低通过抑制细胞周期进程抑制RCC细胞增殖,并通过逆转上皮-间质转化表型抑制RCC细胞迁移和侵袭。NEAT1的下调增加了RCC细胞对索拉非尼的敏感性。机制分析表明,NEAT1作为miR-34a的竞争性海绵,阻止对c-Met的抑制。因此,NEAT1通过miR-34a/c-Met轴促进RCC进展。

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