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A feed-forward loop between lncARSR and YAP activity promotes expansion of renal tumour-initiating cells

Renal tumour-initiating cells (T-ICs) contribute to tumorigenesis, progression and drug resistance of renal cell carcinoma (RCC). However, the underlying mechanism for the propagation of renal T-ICs remains unclear. Here we show that long non-coding RNA lncARSR is upregulated in primary renal T-ICs...

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Detalles Bibliográficos
Autores principales: Qu, Le, Wu, Zhenjie, Li, Yaoming, Xu, Zhipeng, Liu, Bing, Liu, Feng, Bao, Yi, Wu, Dengshuang, Liu, Jiayi, Wang, Anbang, Chu, Xiaoyuan, Sun, Yinghao, Chen, Cheng, Zhang, Zhengyu, Wang, Linhui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133634/
https://www.ncbi.nlm.nih.gov/pubmed/27886176
http://dx.doi.org/10.1038/ncomms12692
Descripción
Sumario:Renal tumour-initiating cells (T-ICs) contribute to tumorigenesis, progression and drug resistance of renal cell carcinoma (RCC). However, the underlying mechanism for the propagation of renal T-ICs remains unclear. Here we show that long non-coding RNA lncARSR is upregulated in primary renal T-ICs and associated with a poor prognosis of clear cell RCCs (ccRCC). Knockdown of lncARSR attenuates the self-renewal, tumorigenicity and metastasis of renal T-ICs. Conversely, forced lncARSR expression enhances T-IC properties of RCC cells. Mechanistically, the binding of lncARSR to YAP impedes LATS1-induced YAP phosphorylation and facilitates YAP nuclear translocation. Reciprocally, YAP/TEAD promotes lncARSR transcription, thus forming a feed-forward circuit. The correlation between lncARSR and YAP is validated in a ccRCC cohort, where the combination of these two parameters exhibits improved prognostic accuracy. Our findings indicate that lncARSR plays a critical role in renal T-ICs propagation and may serve as a prognostic biomarker and potential therapeutic target.