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长链非编码RNA RP11-624L4.1与鼻咽癌不良预后相关,并通过CDK4/6-细胞周期蛋白D1-Rb-E2F1通路促进鼻咽癌增殖。

lncRNA RP11-624L4.1 Is Associated with Unfavorable Prognosis and Promotes Proliferation via the CDK4/6-Cyclin D1-Rb-E2F1 Pathway in NPC.

作者信息

Zhou Liuying, Liu Ruijie, Liang Xujun, Zhang Sai, Bi Wu, Yang Mei, He Yi, Jin Jin, Li Shisheng, Yang Xinming, Fu Junjiang, Zhang Pengfei

机构信息

NHC Key Laboratory of Cancer Proteomics, Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.

National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.

出版信息

Mol Ther Nucleic Acids. 2020 Dec 4;22:1025-1039. doi: 10.1016/j.omtn.2020.10.017. Epub 2020 Oct 15.

Abstract

Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in southern China and southeast Asia. Emerging evidence revealed that long noncoding RNAs (lncRNAs) might play important roles in the development and progression of many cancers, including NPC. The functions and mechanisms of the vast majority of lncRNAs involved in NPC remain unknown. In this study, a novel lncRNA RP11-624L4.1 was identified in NPC tissues using next-generation sequencing. hybridization (ISH) was used to analyze the correlation between RP11-624L4.1 expression and the clinicopathological features or prognosis in NPC patients. RNA-Protein Interaction Prediction (RPISeq) predictions and RNA-binding protein immunoprecipitation (RIP) assays were used to identify RP11-624L4.1's interactions with cyclin-dependent kinase 4 (CDK4). As a result, we found that RP11-624L4.1 is hyper-expressed in NPC tissues, which was associated with unfavorable prognosis and clinicopathological features in NPC. By knocking down and overexpressing RP11-624L4.1, we also found that it promotes the proliferation ability of NPC and through the CDK4/6-Cyclin D1-Rb-E2F1 pathway. Overexpression of CDK4 in knocking down RP11-624L4.1 cells can partially rescue NPC promotion, indicating its role in the RP11-624L4.1-CDK4/6-Cyclin D1-Rb-E2F1 pathway. Taken together, RP11-624L4.1 is required for NPC unfavorable prognosis and proliferation through the CDK4/6-Cyclin D1-Rb-E2F1 pathway, which may be a novel therapeutic target and prognostic in patients with NPC.

摘要

鼻咽癌(NPC)是中国南方和东南亚最常见的恶性肿瘤之一。新出现的证据表明,长链非编码RNA(lncRNAs)可能在包括鼻咽癌在内的许多癌症的发生和发展中发挥重要作用。参与鼻咽癌的绝大多数lncRNAs的功能和机制仍不清楚。在本研究中,使用下一代测序在鼻咽癌组织中鉴定出一种新的lncRNA RP11-624L4.1。采用原位杂交(ISH)分析RP11-624L4.1表达与鼻咽癌患者临床病理特征或预后之间的相关性。使用RNA-蛋白质相互作用预测(RPISeq)预测和RNA结合蛋白免疫沉淀(RIP)试验来鉴定RP11-624L4.1与细胞周期蛋白依赖性激酶4(CDK4)的相互作用。结果,我们发现RP11-624L4.1在鼻咽癌组织中高表达,这与鼻咽癌的不良预后和临床病理特征相关。通过敲低和过表达RP11-624L4.1,我们还发现它通过CDK4/6-Cyclin D1-Rb-E2F1途径促进鼻咽癌的增殖能力。在敲低RP11-624L4.1的细胞中过表达CDK4可以部分挽救对鼻咽癌的促进作用,表明其在RP11-624L4.1-CDK4/6-Cyclin D1-Rb-E2F1途径中的作用。综上所述,RP11-624L4.1通过CDK4/6-Cyclin D1-Rb-E2F1途径参与鼻咽癌的不良预后和增殖,这可能是鼻咽癌患者的一个新的治疗靶点和预后指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d89a/7689037/26f790fee756/fx1.jpg

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