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 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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Biomarkers, Tumor, Carcinoma, Renal Cell, Cell Line, Tumor, Cell Nucleus, Cohort Studies, Disease Progression, Female, Gene Knockdown Techniques, Humans, Kidney, Kidney Neoplasms, Male, Mice, Mice, Inbred BALB C, Mice, Nude, Middle Aged, Neoplastic Stem Cells, Phosphoproteins, Phosphorylation, Prognosis, Protein-Serine-Threonine Kinases, RNA, Long Noncoding, Survival Analysis, Up-Regulation, Xenograft Model Antitumor Assays
Nat Commun
Date: Dec. 25, 2015
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