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

Abstract 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-r...

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Autores principales:	Bowen Zhu, Megan Finch-Edmondson, Kim Whye Leong, Xiaoqian Zhang, Mitheera V., Quy Xiao Xuan Lin, Yaelim Lee, Wei Ting Ng, Huili Guo, Yue Wan, Marius Sudol, Ramanuj DasGupta
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
Acceso en línea:	https://doaj.org/article/4991791ee8144a329868ce14d5a6273d
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spelling	oai:doaj.org-article:4991791ee8144a329868ce14d5a6273d2021-12-05T12:08:26ZLncRNA SFTA1P mediates positive feedback regulation of the Hippo-YAP/TAZ signaling pathway in non-small cell lung cancer10.1038/s41420-021-00761-02058-7716https://doaj.org/article/4991791ee8144a329868ce14d5a6273d2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41420-021-00761-0https://doaj.org/toc/2058-7716Abstract 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.Bowen ZhuMegan Finch-EdmondsonKim Whye LeongXiaoqian ZhangMitheera V.Quy Xiao Xuan LinYaelim LeeWei Ting NgHuili GuoYue WanMarius SudolRamanuj DasGuptaNature Publishing GrouparticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282CytologyQH573-671ENCell Death Discovery, Vol 7, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671 Bowen Zhu Megan Finch-Edmondson Kim Whye Leong Xiaoqian Zhang Mitheera V. Quy Xiao Xuan Lin Yaelim Lee Wei Ting Ng Huili Guo Yue Wan Marius Sudol Ramanuj DasGupta LncRNA SFTA1P mediates positive feedback regulation of the Hippo-YAP/TAZ signaling pathway in non-small cell lung cancer
description	Abstract 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.
format	article
author	Bowen Zhu Megan Finch-Edmondson Kim Whye Leong Xiaoqian Zhang Mitheera V. Quy Xiao Xuan Lin Yaelim Lee Wei Ting Ng Huili Guo Yue Wan Marius Sudol Ramanuj DasGupta
author_facet	Bowen Zhu Megan Finch-Edmondson Kim Whye Leong Xiaoqian Zhang Mitheera V. Quy Xiao Xuan Lin Yaelim Lee Wei Ting Ng Huili Guo Yue Wan Marius Sudol Ramanuj DasGupta
author_sort	Bowen Zhu
title	LncRNA SFTA1P mediates positive feedback regulation of the Hippo-YAP/TAZ signaling pathway in non-small cell lung cancer
title_short	LncRNA SFTA1P mediates positive feedback regulation of the Hippo-YAP/TAZ signaling pathway in non-small cell lung cancer
title_full	LncRNA SFTA1P mediates positive feedback regulation of the Hippo-YAP/TAZ signaling pathway in non-small cell lung cancer
title_fullStr	LncRNA SFTA1P mediates positive feedback regulation of the Hippo-YAP/TAZ signaling pathway in non-small cell lung cancer
title_full_unstemmed	LncRNA SFTA1P mediates positive feedback regulation of the Hippo-YAP/TAZ signaling pathway in non-small cell lung cancer
title_sort	lncrna sfta1p mediates positive feedback regulation of the hippo-yap/taz signaling pathway in non-small cell lung cancer
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/4991791ee8144a329868ce14d5a6273d
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LncRNA SFTA1P mediates positive feedback regulation of the Hippo-YAP/TAZ signaling pathway in non-small cell lung cancer

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