miRNA-200c-3p targets talin-1 to regulate integrin-mediated cell adhesion

Abstract The ability of integrins on the cell surface to mediate cell adhesion to the extracellular matrix ligands is regulated by intracellular signaling cascades. During this signaling process, the talin (TLN) recruited to integrin cytoplasmic tails plays the critical role of the major adaptor pro...

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Autores principales:	Gideon Obeng, Eun Jeong Park, Michael G. Appiah, Eiji Kawamoto, Arong Gaowa, Motomu Shimaoka
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b38ef06bfa9342939c29a80d19cbf190
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spelling	oai:doaj.org-article:b38ef06bfa9342939c29a80d19cbf1902021-11-08T10:47:16ZmiRNA-200c-3p targets talin-1 to regulate integrin-mediated cell adhesion10.1038/s41598-021-01143-32045-2322https://doaj.org/article/b38ef06bfa9342939c29a80d19cbf1902021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01143-3https://doaj.org/toc/2045-2322Abstract The ability of integrins on the cell surface to mediate cell adhesion to the extracellular matrix ligands is regulated by intracellular signaling cascades. During this signaling process, the talin (TLN) recruited to integrin cytoplasmic tails plays the critical role of the major adaptor protein to trigger integrin activation. Thus, intracellular levels of TLN are thought to determine integrin-mediated cellular functions. However, the epigenetic regulation of TLN expression and consequent modulation of integrin activation remain to be elucidated. Bioinformatics analysis led us to consider miR-200c-3p as a TLN1-targeting miRNA. To test this, we have generated miR-200c-3p-overexpressing and miR-200c-3p-underexpressing cell lines, including HEK293T, HCT116, and LNCaP cells. Overexpression of miR-200c-3p resulted in a remarkable decrease in the expression of TLN1, which was associated with the suppression of integrin-mediated cell adhesion to fibronectin. In contrast, the reduction in endogenous miR-200c-3p levels led to increased expression of TLN1 and enhanced cell adhesion to fibronectin and focal adhesion plaques formation. Moreover, miR-200c-3p was found to target TLN1 by binding to its 3′-untranslated region (UTR). Taken together, our data indicate that miR-200c-3p contributes to the regulation of integrin activation and cell adhesion via the targeting of TLN1.Gideon ObengEun Jeong ParkMichael G. AppiahEiji KawamotoArong GaowaMotomu ShimaokaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Gideon Obeng Eun Jeong Park Michael G. Appiah Eiji Kawamoto Arong Gaowa Motomu Shimaoka miRNA-200c-3p targets talin-1 to regulate integrin-mediated cell adhesion
description	Abstract The ability of integrins on the cell surface to mediate cell adhesion to the extracellular matrix ligands is regulated by intracellular signaling cascades. During this signaling process, the talin (TLN) recruited to integrin cytoplasmic tails plays the critical role of the major adaptor protein to trigger integrin activation. Thus, intracellular levels of TLN are thought to determine integrin-mediated cellular functions. However, the epigenetic regulation of TLN expression and consequent modulation of integrin activation remain to be elucidated. Bioinformatics analysis led us to consider miR-200c-3p as a TLN1-targeting miRNA. To test this, we have generated miR-200c-3p-overexpressing and miR-200c-3p-underexpressing cell lines, including HEK293T, HCT116, and LNCaP cells. Overexpression of miR-200c-3p resulted in a remarkable decrease in the expression of TLN1, which was associated with the suppression of integrin-mediated cell adhesion to fibronectin. In contrast, the reduction in endogenous miR-200c-3p levels led to increased expression of TLN1 and enhanced cell adhesion to fibronectin and focal adhesion plaques formation. Moreover, miR-200c-3p was found to target TLN1 by binding to its 3′-untranslated region (UTR). Taken together, our data indicate that miR-200c-3p contributes to the regulation of integrin activation and cell adhesion via the targeting of TLN1.
format	article
author	Gideon Obeng Eun Jeong Park Michael G. Appiah Eiji Kawamoto Arong Gaowa Motomu Shimaoka
author_facet	Gideon Obeng Eun Jeong Park Michael G. Appiah Eiji Kawamoto Arong Gaowa Motomu Shimaoka
author_sort	Gideon Obeng
title	miRNA-200c-3p targets talin-1 to regulate integrin-mediated cell adhesion
title_short	miRNA-200c-3p targets talin-1 to regulate integrin-mediated cell adhesion
title_full	miRNA-200c-3p targets talin-1 to regulate integrin-mediated cell adhesion
title_fullStr	miRNA-200c-3p targets talin-1 to regulate integrin-mediated cell adhesion
title_full_unstemmed	miRNA-200c-3p targets talin-1 to regulate integrin-mediated cell adhesion
title_sort	mirna-200c-3p targets talin-1 to regulate integrin-mediated cell adhesion
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b38ef06bfa9342939c29a80d19cbf190
work_keys_str_mv	AT gideonobeng mirna200c3ptargetstalin1toregulateintegrinmediatedcelladhesion AT eunjeongpark mirna200c3ptargetstalin1toregulateintegrinmediatedcelladhesion AT michaelgappiah mirna200c3ptargetstalin1toregulateintegrinmediatedcelladhesion AT eijikawamoto mirna200c3ptargetstalin1toregulateintegrinmediatedcelladhesion AT aronggaowa mirna200c3ptargetstalin1toregulateintegrinmediatedcelladhesion AT motomushimaoka mirna200c3ptargetstalin1toregulateintegrinmediatedcelladhesion
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miRNA-200c-3p targets talin-1 to regulate integrin-mediated cell adhesion

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