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Alternative Splicing of SMAD4 and Its Function in HaCaT Cells in Response to UVB Irradiation

Alternative splicing is one of the most common mechanisms of human gene regulation and plays a crucial role in increasing the diversity of functional proteins. Many diseases are linked to alternative splicing, especially cancer. SMAD4 is a member of the SMAD family and plays a critical role in media...

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Autores principales: Ullah, Irfan, Liao, Yi, Wan, Rongxue, Tang, Liling, Feng, Jianguo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134820/
https://www.ncbi.nlm.nih.gov/pubmed/30210641
http://dx.doi.org/10.7150/jca.24756
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author Ullah, Irfan
Liao, Yi
Wan, Rongxue
Tang, Liling
Feng, Jianguo
author_facet Ullah, Irfan
Liao, Yi
Wan, Rongxue
Tang, Liling
Feng, Jianguo
author_sort Ullah, Irfan
collection PubMed
description Alternative splicing is one of the most common mechanisms of human gene regulation and plays a crucial role in increasing the diversity of functional proteins. Many diseases are linked to alternative splicing, especially cancer. SMAD4 is a member of the SMAD family and plays a critical role in mediating of TGF-β signal transduction and gene regulatory events. Smad4 is a tumour suppressor and acts as a shuttling protein between nucleus and cytoplasm. The splicing variants of Smad4 have been found in many cancers. The present study performed nested PCR to detect alternative splicing of Smad4 in HaCaT cells lines in response to UVB irradiation. The UVB induced a novel Smad4B isoform that led to decrease the Smad4 expression. The hnRNPA1 splicing factor is responsible for Smad4 alternative splicing in response to UVB. The UVB increased the expression of SF2 and hnRNPA1 Splicing factors. The hnRNPA1 overexpression induced Smad4B by regulating Smad4 alternative splicing. The Smad4B isoform supported the function of Smad4 full length in UVB resistance with certain limitation. The western blot analyses showed that the overexpressed Smad4 full length significantly increased N-cadherin expression while Smad4B overexpression decreased the expression the N-cadherin (P<0.05). Furthermore, overexpression of the isoform in HaCaT cells decreased cell invasion as compared to Smad4 full-length overexpression. These results will be helpful to understand the importance of Smad4 alternative splicing in skin tumorigenesis.
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spelling pubmed-61348202018-09-12 Alternative Splicing of SMAD4 and Its Function in HaCaT Cells in Response to UVB Irradiation Ullah, Irfan Liao, Yi Wan, Rongxue Tang, Liling Feng, Jianguo J Cancer Research Paper Alternative splicing is one of the most common mechanisms of human gene regulation and plays a crucial role in increasing the diversity of functional proteins. Many diseases are linked to alternative splicing, especially cancer. SMAD4 is a member of the SMAD family and plays a critical role in mediating of TGF-β signal transduction and gene regulatory events. Smad4 is a tumour suppressor and acts as a shuttling protein between nucleus and cytoplasm. The splicing variants of Smad4 have been found in many cancers. The present study performed nested PCR to detect alternative splicing of Smad4 in HaCaT cells lines in response to UVB irradiation. The UVB induced a novel Smad4B isoform that led to decrease the Smad4 expression. The hnRNPA1 splicing factor is responsible for Smad4 alternative splicing in response to UVB. The UVB increased the expression of SF2 and hnRNPA1 Splicing factors. The hnRNPA1 overexpression induced Smad4B by regulating Smad4 alternative splicing. The Smad4B isoform supported the function of Smad4 full length in UVB resistance with certain limitation. The western blot analyses showed that the overexpressed Smad4 full length significantly increased N-cadherin expression while Smad4B overexpression decreased the expression the N-cadherin (P<0.05). Furthermore, overexpression of the isoform in HaCaT cells decreased cell invasion as compared to Smad4 full-length overexpression. These results will be helpful to understand the importance of Smad4 alternative splicing in skin tumorigenesis. Ivyspring International Publisher 2018-08-06 /pmc/articles/PMC6134820/ /pubmed/30210641 http://dx.doi.org/10.7150/jca.24756 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Ullah, Irfan
Liao, Yi
Wan, Rongxue
Tang, Liling
Feng, Jianguo
Alternative Splicing of SMAD4 and Its Function in HaCaT Cells in Response to UVB Irradiation
title Alternative Splicing of SMAD4 and Its Function in HaCaT Cells in Response to UVB Irradiation
title_full Alternative Splicing of SMAD4 and Its Function in HaCaT Cells in Response to UVB Irradiation
title_fullStr Alternative Splicing of SMAD4 and Its Function in HaCaT Cells in Response to UVB Irradiation
title_full_unstemmed Alternative Splicing of SMAD4 and Its Function in HaCaT Cells in Response to UVB Irradiation
title_short Alternative Splicing of SMAD4 and Its Function in HaCaT Cells in Response to UVB Irradiation
title_sort alternative splicing of smad4 and its function in hacat cells in response to uvb irradiation
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134820/
https://www.ncbi.nlm.nih.gov/pubmed/30210641
http://dx.doi.org/10.7150/jca.24756
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