Long noncoding RNA MRCCAT1 promotes metastasis of clear cell renal cell carcinoma via inhibiting NPR3 and activating p38-MAPK signaling

Molecular Cancer

Research

Shu-Peng Liu¹  Ming-Ming Jiang²  Ji-Hang Yuan³  Cheng Chen⁴  Deng-Shuang Wu⁵  Zi-Yu Fang⁵  Lin-Hui Wang⁶  Jia-Yi Liu⁶  Jia-Zi Shi⁶  Bing Liu⁶  Yi Bao⁶  Jia-Kuan Li⁷  Le Qu⁸ 

[1] Central laboratory, Changhai Hospital, Second Military Medical University, 200433, Shanghai, China;Clinical laboratory, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 200433, Shanghai, China;Department of Medical Genetics, Second Military Medical University, 200433, Shanghai, China;Department of Medical Oncology, Jinling Hospital, Nanjing University Clinical School of Medicine, 210002, Nanjing, China;Department of Urology, Changhai Hospital, Second Military Medical University, 200433, Shanghai, China;Department of Urology, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, 200003, Shanghai, China;Department of Urology, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, 200003, Shanghai, China;Department of Urology, The 517th Hospital of People’s Liberation Army, 036301, Shanxi, China;Department of Urology, Jinling Hospital, Nanjing University Clinical School of Medicine, 210002, Nanjing, China;

关键词: Clear cell renal cell carcinoma;    Long noncoding RNA;    Metastasis;    MAPK signaling;   

DOI  :  10.1186/s12943-017-0681-0

 received in 2017-02-28, accepted in 2017-06-15,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundRecent evidences showed that long noncoding RNAs (lncRNAs) are frequently dysregulated and play important roles in various cancers. Clear cell renal cell carcinoma (ccRCC) is one of the leading cause of cancer-related death, largely due to the metastasis of ccRCC. However, the clinical significances and roles of lncRNAs in metastatic ccRCC are still unknown.MethodslncRNA expression microarray analysis was performed to search the dysregulated lncRNA in metastatic ccRCC. quantitative real-time PCR was performed to measure the expression of lncRNAs in human ccRCC samples. Gain-of-function and loss-of-function experiments were performed to investigate the biological roles of lncRNAs on ccRCC cell proliferation, migration, invasion and in vivo metastasis. RNA pull-down, RNA immunoprecipitation, chromatin immunoprecipitation, and western blot were performed to explore the molecular mechanisms underlying the functions of lncRNAs.ResultsThe microarray analysis identified a novel lncRNA termed metastatic renal cell carcinoma-associated transcript 1 (MRCCAT1), which is highly expressed in metastatic ccRCC tissues and associated with the metastatic properties of ccRCC. Multivariate Cox regression analysis revealed that MRCCAT1 is an independent prognostic factor for ccRCC patients. Overexpression of MRCCAT1 promotes ccRCC cells proliferation, migration, and invasion. Depletion of MRCCAT1 inhibites ccRCC cells proliferation, migration, and invasion in vitro, and ccRCC metastasis in vivo. Mechanistically, MRCCAT1 represses NPR3 transcription by recruiting PRC2 to NPR3 promoter, and subsequently activates p38-MAPK signaling pathway.ConclusionsMRCCAT1 is a critical lncRNA that promotes ccRCC metastasis via inhibiting NPR3 and activating p38-MAPK signaling. Our results imply that MRCCAT1 could serve as a prognostic biomarker and therapeutic target for ccRCC.

【 授权许可】

CC BY   
© The Author(s). 2017