LncRNA SFTA1P mediates positive feedback regulation of the Hippo-YAP/TAZ signaling pathway in non-small cell lung cancer.

Autor: Zhu B; Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), Singapore, 138672, Singapore.; Department of Physiology, NUS Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117593, Singapore., Finch-Edmondson M; Mechanobiology Institute (MBI), National University of Singapore, Singapore, 117411, Singapore., Leong KW; Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), Singapore, 138672, Singapore.; Department of Physiology, NUS Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117593, Singapore., Zhang X; Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), Singapore, 138672, Singapore., V M; Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), Singapore, 138672, Singapore.; Department of Physiology, NUS Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117593, Singapore., Lin QXX; Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore., Lee Y; Mechanobiology Institute (MBI), National University of Singapore, Singapore, 117411, Singapore., Ng WT; Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, 138673, Singapore., Guo H; Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, 138673, Singapore., Wan Y; Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), Singapore, 138672, Singapore., Sudol M; Department of Physiology, NUS Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117593, Singapore.; Mechanobiology Institute (MBI), National University of Singapore, Singapore, 117411, Singapore.; Icahn School of Medicine at Mount Sinai, New York City, NY, 10029, USA., DasGupta R; Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), Singapore, 138672, Singapore. dasguptar@gis.a-star.edu.sg.
Jazyk: angličtina
Zdroj: Cell death discovery [Cell Death Discov] 2021 Nov 29; Vol. 7 (1), pp. 369. Date of Electronic Publication: 2021 Nov 29.
DOI: 10.1038/s41420-021-00761-0
Abstrakt: Long non-coding RNAs (lncRNAs) regulate numerous biological processes involved in both development and carcinogenesis. Hippo-YAP/TAZ signaling, a critical pathway responsible for organ size control, is often dysregulated in a variety of cancers. However, the nature and function of YAP/TAZ-regulated lncRNAs during tumorigenesis remain largely unexplored. By profiling YAP/TAZ-regulated lncRNAs, we identified SFTA1P as a novel transcriptional target and a positive feedback regulator of YAP/TAZ signaling. Using non-small cell lung cancer (NSCLC) cell lines, we show that SFTA1P is transcriptionally activated by YAP/TAZ in a TEAD-dependent manner. Functionally, knockdown of SFTA1P in NSCLC cell lines inhibited proliferation, induced programmed cell death, and compromised their tumorigenic potential. Mechanistically, SFTA1P knockdown decreased TAZ protein abundance and consequently, the expression of YAP/TAZ transcriptional targets. We provide evidence that this phenomenon could potentially be mediated via its interaction with TAZ mRNA to regulate TAZ translation. Our results reveal SFTA1P as a positive feedback regulator of Hippo-YAP/TAZ signaling, which may serve as the molecular basis for lncRNA-based therapies against YAP/TAZ-driven cancers.
(© 2021. The Author(s).)
Databáze: MEDLINE
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