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

被引:27
作者
Zhou, Liuying [1 ,2 ]
Liu, Ruijie [1 ,2 ]
Liang, Xujun [1 ,2 ]
Zhang, Sai [1 ,2 ]
Bi, Wu [1 ,2 ]
Yang, Mei [1 ,2 ]
He, Yi [1 ,2 ]
Jin, Jin [1 ,2 ]
Li, Shisheng [3 ]
Yang, Xinming [3 ]
Fu, Junjiang [4 ]
Zhang, Pengfei [1 ,2 ]
机构
[1] Cent South Univ, Xiangya Hosp, Dept Oncol, NHC Key Lab Canc Prote, Changsha 410008, Hunan, Peoples R China
[2] Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha 410008, Hunan, Peoples R China
[3] Cent South Univ, Xiangya Hosp 2, Dept Otolaryngol Head & Neck Surg, Changsha 410011, Hunan, Peoples R China
[4] Southwest Med Univ, Res Ctr Preclin Med, Key Lab Epigenet & Oncol, Luzhou 646000, Sichuan, Peoples R China
基金
中国国家自然科学基金;
关键词
CDK4; CDK4/Cyclin D1/Rb/E2F signaling pathway; in situ hybridization; lncRNA RP11-624L4.1; nasopharyngeal carcinoma; proliferation; RNA-binding protein immunoprecipitation;
D O I
10.1016/j.omtn.2020.10.017
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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. In situ 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 in vitro and in vivo 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.
引用
收藏
页码:1025 / 1039
页数:15
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