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Pinin interacts with C-terminal binding proteins for RNA alternative splicing and epithelial cell identity of human ovarian cancer cells
Unlike many other human solid tumors, ovarian tumors express many epithelial markers at a high level for cell growth and local invasion. The phosphoprotein Pinin plays a key role in epithelial cell identity. We showed that clinical ovarian tumors and ovarian cancer cell lines express a high level of...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4905481/ https://www.ncbi.nlm.nih.gov/pubmed/26871283 http://dx.doi.org/10.18632/oncotarget.7242 |
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author | Zhang, Yanli Kwok, Jamie Sui-Lam Choi, Pui-Wah Liu, Minghua Yang, Junzheng Singh, Margit Ng, Shu-Kay Welch, William R. Muto, Michael G. Tsui, Stephen KW Sugrue, Stephen P. Berkowitz, Ross S. Ng, Shu-Wing |
author_facet | Zhang, Yanli Kwok, Jamie Sui-Lam Choi, Pui-Wah Liu, Minghua Yang, Junzheng Singh, Margit Ng, Shu-Kay Welch, William R. Muto, Michael G. Tsui, Stephen KW Sugrue, Stephen P. Berkowitz, Ross S. Ng, Shu-Wing |
author_sort | Zhang, Yanli |
collection | PubMed |
description | Unlike many other human solid tumors, ovarian tumors express many epithelial markers at a high level for cell growth and local invasion. The phosphoprotein Pinin plays a key role in epithelial cell identity. We showed that clinical ovarian tumors and ovarian cancer cell lines express a high level of Pinin when compared with normal ovarian tissues and immortalized normal ovarian surface epithelial cell lines. Pinin co-localized and physically interacted with transcriptional corepressor C-terminal binding proteins, CtBP1 and CtBP2, in the nuclei of cancer cells. Knockdown of Pinin in ovarian cancer cells resulted in specific reduction of CtBP1 protein expression, cell adhesion, anchorage-independent growth, and increased drug sensitivity. Whole transcriptomic comparison of next-generation RNA sequencing data between control ovarian cancer cell lines and cancer cell lines with respective knockdown of Pinin, CtBP1, and CtBP2 expression also showed reduced expression of CtBP1 mRNA in the Pinin knockdown cell lines. The Pinin knockdown cell lines shared significant overlap of differentially expressed genes and RNA splicing aberrations with CtBP1 knockdown and in a lesser degree with CtBP2 knockdown cancer cells. Hence, Pinin and CtBP are oncotargets that closely interact with each other to regulate transcription and pre-mRNA alternative splicing and promote cell adhesion and other epithelial characteristics of ovarian cancer cells. |
format | Online Article Text |
id | pubmed-4905481 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-49054812016-06-24 Pinin interacts with C-terminal binding proteins for RNA alternative splicing and epithelial cell identity of human ovarian cancer cells Zhang, Yanli Kwok, Jamie Sui-Lam Choi, Pui-Wah Liu, Minghua Yang, Junzheng Singh, Margit Ng, Shu-Kay Welch, William R. Muto, Michael G. Tsui, Stephen KW Sugrue, Stephen P. Berkowitz, Ross S. Ng, Shu-Wing Oncotarget Research Paper Unlike many other human solid tumors, ovarian tumors express many epithelial markers at a high level for cell growth and local invasion. The phosphoprotein Pinin plays a key role in epithelial cell identity. We showed that clinical ovarian tumors and ovarian cancer cell lines express a high level of Pinin when compared with normal ovarian tissues and immortalized normal ovarian surface epithelial cell lines. Pinin co-localized and physically interacted with transcriptional corepressor C-terminal binding proteins, CtBP1 and CtBP2, in the nuclei of cancer cells. Knockdown of Pinin in ovarian cancer cells resulted in specific reduction of CtBP1 protein expression, cell adhesion, anchorage-independent growth, and increased drug sensitivity. Whole transcriptomic comparison of next-generation RNA sequencing data between control ovarian cancer cell lines and cancer cell lines with respective knockdown of Pinin, CtBP1, and CtBP2 expression also showed reduced expression of CtBP1 mRNA in the Pinin knockdown cell lines. The Pinin knockdown cell lines shared significant overlap of differentially expressed genes and RNA splicing aberrations with CtBP1 knockdown and in a lesser degree with CtBP2 knockdown cancer cells. Hence, Pinin and CtBP are oncotargets that closely interact with each other to regulate transcription and pre-mRNA alternative splicing and promote cell adhesion and other epithelial characteristics of ovarian cancer cells. Impact Journals LLC 2016-02-08 /pmc/articles/PMC4905481/ /pubmed/26871283 http://dx.doi.org/10.18632/oncotarget.7242 Text en Copyright: © 2016 Zhang et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Zhang, Yanli Kwok, Jamie Sui-Lam Choi, Pui-Wah Liu, Minghua Yang, Junzheng Singh, Margit Ng, Shu-Kay Welch, William R. Muto, Michael G. Tsui, Stephen KW Sugrue, Stephen P. Berkowitz, Ross S. Ng, Shu-Wing Pinin interacts with C-terminal binding proteins for RNA alternative splicing and epithelial cell identity of human ovarian cancer cells |
title | Pinin interacts with C-terminal binding proteins for RNA alternative splicing and epithelial cell identity of human ovarian cancer cells |
title_full | Pinin interacts with C-terminal binding proteins for RNA alternative splicing and epithelial cell identity of human ovarian cancer cells |
title_fullStr | Pinin interacts with C-terminal binding proteins for RNA alternative splicing and epithelial cell identity of human ovarian cancer cells |
title_full_unstemmed | Pinin interacts with C-terminal binding proteins for RNA alternative splicing and epithelial cell identity of human ovarian cancer cells |
title_short | Pinin interacts with C-terminal binding proteins for RNA alternative splicing and epithelial cell identity of human ovarian cancer cells |
title_sort | pinin interacts with c-terminal binding proteins for rna alternative splicing and epithelial cell identity of human ovarian cancer cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4905481/ https://www.ncbi.nlm.nih.gov/pubmed/26871283 http://dx.doi.org/10.18632/oncotarget.7242 |
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