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High expression of PTBP1 promote invasion of colorectal cancer by alternative splicing of cortactin

Polypyrimidine tract-binding protein 1 (PTBP1) involving in almost all steps of mRNA regulation including alternative splicing metabolism during tumorigenesis due to its RNA-binding activity. Initially, we found that high expressed PTBP1 and poor prognosis was interrelated in colorectal cancer (CRC)...

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Autores principales: Wang, Zhi-na, Liu, Dan, Yin, Bin, Ju, Wen-yi, Qiu, Hui-zhong, Xiao, Yi, Chen, Yuan-jia, Peng, Xiao-zhong, Lu, Chong-mei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482648/
https://www.ncbi.nlm.nih.gov/pubmed/28404950
http://dx.doi.org/10.18632/oncotarget.15873
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author Wang, Zhi-na
Liu, Dan
Yin, Bin
Ju, Wen-yi
Qiu, Hui-zhong
Xiao, Yi
Chen, Yuan-jia
Peng, Xiao-zhong
Lu, Chong-mei
author_facet Wang, Zhi-na
Liu, Dan
Yin, Bin
Ju, Wen-yi
Qiu, Hui-zhong
Xiao, Yi
Chen, Yuan-jia
Peng, Xiao-zhong
Lu, Chong-mei
author_sort Wang, Zhi-na
collection PubMed
description Polypyrimidine tract-binding protein 1 (PTBP1) involving in almost all steps of mRNA regulation including alternative splicing metabolism during tumorigenesis due to its RNA-binding activity. Initially, we found that high expressed PTBP1 and poor prognosis was interrelated in colorectal cancer (CRC) patients with stages II and III CRC, which widely different in prognosis and treatment, by immunohistochemistry. PTBP1 was also upregulated in colon cancer cell lines. In our study, knockdown of PTBP1 by siRNA transfection decreased cell proliferation and invasion in vitro. Denovirus shRNA knockdown of PTBP1 inhibited colorectal cancer growth in vivo. Furthermore, PTBP1 regulates alternative splicing of many target genes involving in tumorgenesis in colon cancer cells. We confirmed that the splicing of cortactin exon 11 which was only contained in cortactin isoform-a, as a PTBP1 target. Knockdown of PTBP1 decreased the expression of cortactin isoform-a by exclusion of exon 11. Also the mRNA levels of PTBP1 and cortactin isoform-a were cooperatively expressed in colorectal cancer tissues. Knocking down cortactin isoform-a significantly decreased cell migration and invasion in colorectal cancer cells. Overexpression of cortactin isoform-a could rescue PTBP1-knockdown effect of cell motility. In summary the study revealed that PTBP1 facilitates colorectal cancer migration and invasion activities by inclusion of cortactin exon 11.
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spelling pubmed-54826482017-06-27 High expression of PTBP1 promote invasion of colorectal cancer by alternative splicing of cortactin Wang, Zhi-na Liu, Dan Yin, Bin Ju, Wen-yi Qiu, Hui-zhong Xiao, Yi Chen, Yuan-jia Peng, Xiao-zhong Lu, Chong-mei Oncotarget Research Paper Polypyrimidine tract-binding protein 1 (PTBP1) involving in almost all steps of mRNA regulation including alternative splicing metabolism during tumorigenesis due to its RNA-binding activity. Initially, we found that high expressed PTBP1 and poor prognosis was interrelated in colorectal cancer (CRC) patients with stages II and III CRC, which widely different in prognosis and treatment, by immunohistochemistry. PTBP1 was also upregulated in colon cancer cell lines. In our study, knockdown of PTBP1 by siRNA transfection decreased cell proliferation and invasion in vitro. Denovirus shRNA knockdown of PTBP1 inhibited colorectal cancer growth in vivo. Furthermore, PTBP1 regulates alternative splicing of many target genes involving in tumorgenesis in colon cancer cells. We confirmed that the splicing of cortactin exon 11 which was only contained in cortactin isoform-a, as a PTBP1 target. Knockdown of PTBP1 decreased the expression of cortactin isoform-a by exclusion of exon 11. Also the mRNA levels of PTBP1 and cortactin isoform-a were cooperatively expressed in colorectal cancer tissues. Knocking down cortactin isoform-a significantly decreased cell migration and invasion in colorectal cancer cells. Overexpression of cortactin isoform-a could rescue PTBP1-knockdown effect of cell motility. In summary the study revealed that PTBP1 facilitates colorectal cancer migration and invasion activities by inclusion of cortactin exon 11. Impact Journals LLC 2017-03-03 /pmc/articles/PMC5482648/ /pubmed/28404950 http://dx.doi.org/10.18632/oncotarget.15873 Text en Copyright: © 2017 Wang et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Wang, Zhi-na
Liu, Dan
Yin, Bin
Ju, Wen-yi
Qiu, Hui-zhong
Xiao, Yi
Chen, Yuan-jia
Peng, Xiao-zhong
Lu, Chong-mei
High expression of PTBP1 promote invasion of colorectal cancer by alternative splicing of cortactin
title High expression of PTBP1 promote invasion of colorectal cancer by alternative splicing of cortactin
title_full High expression of PTBP1 promote invasion of colorectal cancer by alternative splicing of cortactin
title_fullStr High expression of PTBP1 promote invasion of colorectal cancer by alternative splicing of cortactin
title_full_unstemmed High expression of PTBP1 promote invasion of colorectal cancer by alternative splicing of cortactin
title_short High expression of PTBP1 promote invasion of colorectal cancer by alternative splicing of cortactin
title_sort high expression of ptbp1 promote invasion of colorectal cancer by alternative splicing of cortactin
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482648/
https://www.ncbi.nlm.nih.gov/pubmed/28404950
http://dx.doi.org/10.18632/oncotarget.15873
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