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

Le Qu, Zhenjie Wu, Yaoming Li, Zhipeng Xu, Bing Liu, Feng Liu, Yi Bao, Dengshuang Wu, Jiayi Liu, Anbang Wang, Xiaoyuan Chu, Yinghao Sun, Cheng Chen (), Zhengyu Zhang () and Linhui Wang ()
Additional contact information
Le Qu: Jinling Hospital, Nanjing University Clinical School of Medicine
Zhenjie Wu: Changzheng Hospital, Second Military Medical University
Yaoming Li: Changhai Hospital, Second Military Medical University
Zhipeng Xu: Changzheng Hospital, Second Military Medical University
Bing Liu: Changzheng Hospital, Second Military Medical University
Feng Liu: Obstetrics and Gynecology of Navy PLA General Hospital
Yi Bao: Changzheng Hospital, Second Military Medical University
Dengshuang Wu: Changzheng Hospital, Second Military Medical University
Jiayi Liu: Changzheng Hospital, Second Military Medical University
Anbang Wang: Changzheng Hospital, Second Military Medical University
Xiaoyuan Chu: Jinling Hospital, Nanjing University Clinical School of Medicine
Yinghao Sun: Changhai Hospital, Second Military Medical University
Cheng Chen: Jinling Hospital, Nanjing University Clinical School of Medicine
Zhengyu Zhang: Jinling Hospital, Nanjing University Clinical School of Medicine
Linhui Wang: Changzheng Hospital, Second Military Medical University

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: Abstract 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.

Date: 2016
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms12692 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12692

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms12692

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().