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TMEM16A alternative splicing coordination in breast cancer

BACKGROUND: TMEM16A, also known as Anoctamin-1, is a calcium-activated chloride channel gene overexpressed in many tumors. The role of TMEM16A in cancer is not completely understood and no data are available regarding the potential tumorigenic properties of the multiple isoforms generated by alterna...

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Autores principales: Ubby, Ifeoma, Bussani, Erica, Colonna, Antonio, Stacul, Giuseppe, Locatelli, Martina, Scudieri, Paolo, Galietta, Luis, Pagani, Franco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728142/
https://www.ncbi.nlm.nih.gov/pubmed/23866066
http://dx.doi.org/10.1186/1476-4598-12-75
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author Ubby, Ifeoma
Bussani, Erica
Colonna, Antonio
Stacul, Giuseppe
Locatelli, Martina
Scudieri, Paolo
Galietta, Luis
Pagani, Franco
author_facet Ubby, Ifeoma
Bussani, Erica
Colonna, Antonio
Stacul, Giuseppe
Locatelli, Martina
Scudieri, Paolo
Galietta, Luis
Pagani, Franco
author_sort Ubby, Ifeoma
collection PubMed
description BACKGROUND: TMEM16A, also known as Anoctamin-1, is a calcium-activated chloride channel gene overexpressed in many tumors. The role of TMEM16A in cancer is not completely understood and no data are available regarding the potential tumorigenic properties of the multiple isoforms generated by alternative splicing (AS). METHODS: We evaluated TMEM16A AS pattern, isoforms distribution and Splicing Coordination (SC), in normal tissues and breast cancers, through a semi-quantitative PCR-assay that amplifies transcripts across three AS exons, 6b, 13 and 15. RESULTS: In breast cancer, we did not observe an association either to AS of individual exons or to specific TMEM16A isoforms, and induced expression of the most common isoforms present in tumors in the HEK293 Flp-In Tet-ON system had no effect on cellular proliferation and migration. The analysis of splicing coordination, a mechanism that regulates AS of distant exons, showed a preferential association of exon 6b and 15 in several normal tissues and tumors: isoforms that predominantly include exon 6b tend to exclude exon 15 and vice versa. Interestingly, we found an increase in SC in breast tumors compared to matched normal tissues. CONCLUSIONS: As the different TMEM16A isoforms do not affect proliferation or migration and do not associate with tumors, our results suggest that the resulting channel activities are not directly involved in cell growth and motility. Conversely, the observed increase in SC in breast tumors suggests that the maintenance of the regulatory mechanism that coordinates distant alternative spliced exons in multiple genes other than TMEM16A is necessary for cancer cell viability.
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spelling pubmed-37281422013-07-31 TMEM16A alternative splicing coordination in breast cancer Ubby, Ifeoma Bussani, Erica Colonna, Antonio Stacul, Giuseppe Locatelli, Martina Scudieri, Paolo Galietta, Luis Pagani, Franco Mol Cancer Research BACKGROUND: TMEM16A, also known as Anoctamin-1, is a calcium-activated chloride channel gene overexpressed in many tumors. The role of TMEM16A in cancer is not completely understood and no data are available regarding the potential tumorigenic properties of the multiple isoforms generated by alternative splicing (AS). METHODS: We evaluated TMEM16A AS pattern, isoforms distribution and Splicing Coordination (SC), in normal tissues and breast cancers, through a semi-quantitative PCR-assay that amplifies transcripts across three AS exons, 6b, 13 and 15. RESULTS: In breast cancer, we did not observe an association either to AS of individual exons or to specific TMEM16A isoforms, and induced expression of the most common isoforms present in tumors in the HEK293 Flp-In Tet-ON system had no effect on cellular proliferation and migration. The analysis of splicing coordination, a mechanism that regulates AS of distant exons, showed a preferential association of exon 6b and 15 in several normal tissues and tumors: isoforms that predominantly include exon 6b tend to exclude exon 15 and vice versa. Interestingly, we found an increase in SC in breast tumors compared to matched normal tissues. CONCLUSIONS: As the different TMEM16A isoforms do not affect proliferation or migration and do not associate with tumors, our results suggest that the resulting channel activities are not directly involved in cell growth and motility. Conversely, the observed increase in SC in breast tumors suggests that the maintenance of the regulatory mechanism that coordinates distant alternative spliced exons in multiple genes other than TMEM16A is necessary for cancer cell viability. BioMed Central 2013-07-16 /pmc/articles/PMC3728142/ /pubmed/23866066 http://dx.doi.org/10.1186/1476-4598-12-75 Text en Copyright © 2013 Ubby et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Ubby, Ifeoma
Bussani, Erica
Colonna, Antonio
Stacul, Giuseppe
Locatelli, Martina
Scudieri, Paolo
Galietta, Luis
Pagani, Franco
TMEM16A alternative splicing coordination in breast cancer
title TMEM16A alternative splicing coordination in breast cancer
title_full TMEM16A alternative splicing coordination in breast cancer
title_fullStr TMEM16A alternative splicing coordination in breast cancer
title_full_unstemmed TMEM16A alternative splicing coordination in breast cancer
title_short TMEM16A alternative splicing coordination in breast cancer
title_sort tmem16a alternative splicing coordination in breast cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728142/
https://www.ncbi.nlm.nih.gov/pubmed/23866066
http://dx.doi.org/10.1186/1476-4598-12-75
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