A miR-375/YAP axis regulates neuroendocrine differentiation and tumorigenesis in lung carcinoid cells

Abstract Lung carcinoids are variably aggressive and mechanistically understudied neuroendocrine neoplasms (NENs). Here, we identified and elucidated the function of a miR-375/yes-associated protein (YAP) axis in lung carcinoid (H727) cells. miR-375 and YAP are respectively high and low expressed in...

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Autores principales:	Xiaojing Yang, Jina Nanayakkara, Duncan Claypool, Sadegh Saghafinia, Justin J. M. Wong, Minqi Xu, Xiantao Wang, Christopher J. B. Nicol, Iacovos P. Michael, Markus Hafner, Xiaolong Yang, Neil Renwick
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/72661e3a38244d87bdf71ce5806af456
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spelling	oai:doaj.org-article:72661e3a38244d87bdf71ce5806af4562021-12-02T16:49:46ZA miR-375/YAP axis regulates neuroendocrine differentiation and tumorigenesis in lung carcinoid cells10.1038/s41598-021-89855-42045-2322https://doaj.org/article/72661e3a38244d87bdf71ce5806af4562021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89855-4https://doaj.org/toc/2045-2322Abstract Lung carcinoids are variably aggressive and mechanistically understudied neuroendocrine neoplasms (NENs). Here, we identified and elucidated the function of a miR-375/yes-associated protein (YAP) axis in lung carcinoid (H727) cells. miR-375 and YAP are respectively high and low expressed in wild-type H727 cells. Following lentiviral CRISPR/Cas9-mediated miR-375 depletion, we identified distinct transcriptomic changes including dramatic YAP upregulation. We also observed a significant decrease in neuroendocrine differentiation and substantial reductions in cell proliferation, transformation, and tumor growth in cell culture and xenograft mouse disease models. Similarly, YAP overexpression resulted in distinct and partially overlapping transcriptomic changes, phenocopying the effects of miR-375 depletion in the same models as above. Transient YAP knockdown in miR-375-depleted cells reversed the effects of miR-375 on neuroendocrine differentiation and cell proliferation. Pathways analysis and confirmatory real-time PCR studies of shared dysregulated target genes indicate that this axis controls neuroendocrine related functions such as neural differentiation, exocytosis, and secretion. Taken together, we provide compelling evidence that a miR-375/YAP axis is a critical mediator of neuroendocrine differentiation and tumorigenesis in lung carcinoid cells.Xiaojing YangJina NanayakkaraDuncan ClaypoolSadegh SaghafiniaJustin J. M. WongMinqi XuXiantao WangChristopher J. B. NicolIacovos P. MichaelMarkus HafnerXiaolong YangNeil RenwickNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xiaojing Yang Jina Nanayakkara Duncan Claypool Sadegh Saghafinia Justin J. M. Wong Minqi Xu Xiantao Wang Christopher J. B. Nicol Iacovos P. Michael Markus Hafner Xiaolong Yang Neil Renwick A miR-375/YAP axis regulates neuroendocrine differentiation and tumorigenesis in lung carcinoid cells
description	Abstract Lung carcinoids are variably aggressive and mechanistically understudied neuroendocrine neoplasms (NENs). Here, we identified and elucidated the function of a miR-375/yes-associated protein (YAP) axis in lung carcinoid (H727) cells. miR-375 and YAP are respectively high and low expressed in wild-type H727 cells. Following lentiviral CRISPR/Cas9-mediated miR-375 depletion, we identified distinct transcriptomic changes including dramatic YAP upregulation. We also observed a significant decrease in neuroendocrine differentiation and substantial reductions in cell proliferation, transformation, and tumor growth in cell culture and xenograft mouse disease models. Similarly, YAP overexpression resulted in distinct and partially overlapping transcriptomic changes, phenocopying the effects of miR-375 depletion in the same models as above. Transient YAP knockdown in miR-375-depleted cells reversed the effects of miR-375 on neuroendocrine differentiation and cell proliferation. Pathways analysis and confirmatory real-time PCR studies of shared dysregulated target genes indicate that this axis controls neuroendocrine related functions such as neural differentiation, exocytosis, and secretion. Taken together, we provide compelling evidence that a miR-375/YAP axis is a critical mediator of neuroendocrine differentiation and tumorigenesis in lung carcinoid cells.
format	article
author	Xiaojing Yang Jina Nanayakkara Duncan Claypool Sadegh Saghafinia Justin J. M. Wong Minqi Xu Xiantao Wang Christopher J. B. Nicol Iacovos P. Michael Markus Hafner Xiaolong Yang Neil Renwick
author_facet	Xiaojing Yang Jina Nanayakkara Duncan Claypool Sadegh Saghafinia Justin J. M. Wong Minqi Xu Xiantao Wang Christopher J. B. Nicol Iacovos P. Michael Markus Hafner Xiaolong Yang Neil Renwick
author_sort	Xiaojing Yang
title	A miR-375/YAP axis regulates neuroendocrine differentiation and tumorigenesis in lung carcinoid cells
title_short	A miR-375/YAP axis regulates neuroendocrine differentiation and tumorigenesis in lung carcinoid cells
title_full	A miR-375/YAP axis regulates neuroendocrine differentiation and tumorigenesis in lung carcinoid cells
title_fullStr	A miR-375/YAP axis regulates neuroendocrine differentiation and tumorigenesis in lung carcinoid cells
title_full_unstemmed	A miR-375/YAP axis regulates neuroendocrine differentiation and tumorigenesis in lung carcinoid cells
title_sort	mir-375/yap axis regulates neuroendocrine differentiation and tumorigenesis in lung carcinoid cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/72661e3a38244d87bdf71ce5806af456
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A miR-375/YAP axis regulates neuroendocrine differentiation and tumorigenesis in lung carcinoid cells

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