Annexin A1 down-regulation in head and neck squamous cell carcinoma is mediated via transcriptional control with direct involvement of miR-196a/b

Abstract Annexin A1 (ANXA1) down-regulation is an early and frequent event in the development of head and neck squamous cell carcinomas (HNSCC). In an attempt to identify the underlying mechanisms of reduced ANXA1 protein expression, this study investigated ANXA1 mRNA expression in HNSCC specimens b...

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Autores principales:	Saúl Álvarez-Teijeiro, Sofía T. Menéndez, M. Ángeles Villaronga, Emma Pena-Alonso, Juan P. Rodrigo, Reginald O. Morgan, Rocío Granda-Díaz, Cecilia Salom, M. Pilar Fernandez, Juana M. García-Pedrero
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/139fd7c9cb3b40c9a0f51e3bee0b9862
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spelling	oai:doaj.org-article:139fd7c9cb3b40c9a0f51e3bee0b98622021-12-02T12:32:08ZAnnexin A1 down-regulation in head and neck squamous cell carcinoma is mediated via transcriptional control with direct involvement of miR-196a/b10.1038/s41598-017-07169-w2045-2322https://doaj.org/article/139fd7c9cb3b40c9a0f51e3bee0b98622017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07169-whttps://doaj.org/toc/2045-2322Abstract Annexin A1 (ANXA1) down-regulation is an early and frequent event in the development of head and neck squamous cell carcinomas (HNSCC). In an attempt to identify the underlying mechanisms of reduced ANXA1 protein expression, this study investigated ANXA1 mRNA expression in HNSCC specimens by both in situ hybridization and RT-qPCR. Results showed a perfect concordance between the pattern of ANXA1 mRNA and protein detected by immunofluorescence in tumors, precancerous lesions and normal epithelia, reflecting that ANXA1 down-regulation occurs at transcriptional level. We also found that both miR-196a and miR-196b levels inversely correlated with ANXA1 mRNA levels in paired HNSCC tissue samples and patient-matched normal mucosa. In addition, endogenous levels of ANXA1 mRNA and protein were consistently and significantly down-regulated upon miR-196a and miR-196b over-expression in various HNSCC-derived cell lines. The direct interaction of both mature miR-196a and miR-196b was further confirmed by transfection with Anxa1 3′UTR constructs. Combined bioinformatics and functional analysis of ANXA1 promoter activity contributed to identify key regions and potential mediators of ANXA1 transcriptional control. This study unveils that, in addition to miR-196a, miR-196b also directly targets ANXA1 in HNSCC.Saúl Álvarez-TeijeiroSofía T. MenéndezM. Ángeles VillarongaEmma Pena-AlonsoJuan P. RodrigoReginald O. MorganRocío Granda-DíazCecilia SalomM. Pilar FernandezJuana M. García-PedreroNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Saúl Álvarez-Teijeiro Sofía T. Menéndez M. Ángeles Villaronga Emma Pena-Alonso Juan P. Rodrigo Reginald O. Morgan Rocío Granda-Díaz Cecilia Salom M. Pilar Fernandez Juana M. García-Pedrero Annexin A1 down-regulation in head and neck squamous cell carcinoma is mediated via transcriptional control with direct involvement of miR-196a/b
description	Abstract Annexin A1 (ANXA1) down-regulation is an early and frequent event in the development of head and neck squamous cell carcinomas (HNSCC). In an attempt to identify the underlying mechanisms of reduced ANXA1 protein expression, this study investigated ANXA1 mRNA expression in HNSCC specimens by both in situ hybridization and RT-qPCR. Results showed a perfect concordance between the pattern of ANXA1 mRNA and protein detected by immunofluorescence in tumors, precancerous lesions and normal epithelia, reflecting that ANXA1 down-regulation occurs at transcriptional level. We also found that both miR-196a and miR-196b levels inversely correlated with ANXA1 mRNA levels in paired HNSCC tissue samples and patient-matched normal mucosa. In addition, endogenous levels of ANXA1 mRNA and protein were consistently and significantly down-regulated upon miR-196a and miR-196b over-expression in various HNSCC-derived cell lines. The direct interaction of both mature miR-196a and miR-196b was further confirmed by transfection with Anxa1 3′UTR constructs. Combined bioinformatics and functional analysis of ANXA1 promoter activity contributed to identify key regions and potential mediators of ANXA1 transcriptional control. This study unveils that, in addition to miR-196a, miR-196b also directly targets ANXA1 in HNSCC.
format	article
author	Saúl Álvarez-Teijeiro Sofía T. Menéndez M. Ángeles Villaronga Emma Pena-Alonso Juan P. Rodrigo Reginald O. Morgan Rocío Granda-Díaz Cecilia Salom M. Pilar Fernandez Juana M. García-Pedrero
author_facet	Saúl Álvarez-Teijeiro Sofía T. Menéndez M. Ángeles Villaronga Emma Pena-Alonso Juan P. Rodrigo Reginald O. Morgan Rocío Granda-Díaz Cecilia Salom M. Pilar Fernandez Juana M. García-Pedrero
author_sort	Saúl Álvarez-Teijeiro
title	Annexin A1 down-regulation in head and neck squamous cell carcinoma is mediated via transcriptional control with direct involvement of miR-196a/b
title_short	Annexin A1 down-regulation in head and neck squamous cell carcinoma is mediated via transcriptional control with direct involvement of miR-196a/b
title_full	Annexin A1 down-regulation in head and neck squamous cell carcinoma is mediated via transcriptional control with direct involvement of miR-196a/b
title_fullStr	Annexin A1 down-regulation in head and neck squamous cell carcinoma is mediated via transcriptional control with direct involvement of miR-196a/b
title_full_unstemmed	Annexin A1 down-regulation in head and neck squamous cell carcinoma is mediated via transcriptional control with direct involvement of miR-196a/b
title_sort	annexin a1 down-regulation in head and neck squamous cell carcinoma is mediated via transcriptional control with direct involvement of mir-196a/b
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/139fd7c9cb3b40c9a0f51e3bee0b9862
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Annexin A1 down-regulation in head and neck squamous cell carcinoma is mediated via transcriptional control with direct involvement of miR-196a/b

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