Pinin interacts with C-terminal binding proteins for RNA alternative splicing and epithelial cell identity of human ovarian cancer cells
| Autor: | Shu-Kay Ng, Stephen P. Sugrue, Stephen Kw Tsui, William R. Welch, Michael G. Muto, Junzheng Yang, Pui-Wah Choi, Minghua Liu, Margit Singh, Ross S. Berkowitz, Shu-Wing Ng, Yanli Zhang, Jamie Sui-Lam Kwok |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
RNA metabolism Gene knockdown Pathology medicine.medical_specialty Cell adhesion molecule Cell growth Alternative splicing cell adhesion RNA sequencing Biology medicine.disease_cause medicine.disease 03 medical and health sciences tumorigenesis 030104 developmental biology ovarian cancer Oncology Cancer cell medicine Cancer research Carcinogenesis Cell adhesion Ovarian cancer Research Paper |
| Zdroj: | Oncotarget ResearcherID |
| ISSN: | 1949-2553 |
| Popis: | // Yanli Zhang 1 , Jamie Sui-Lam Kwok 2 , Pui-Wah Choi 1 , Minghua Liu 2 , Junzheng Yang 1 , Margit Singh 1 , Shu-Kay Ng 4 , William R. Welch 5 , Michael G. Muto 1 , Stephen KW Tsui 2 , Stephen P. Sugrue 3 , Ross S. Berkowitz 1 , Shu-Wing Ng 1 1 Laboratory of Gynecologic Oncology, Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, MA, USA 2 School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong 3 Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, FL, USA 4 School of Medicine and Menzies Health Institute Queensland, Griffith University, Meadowbrook, Australia 5 Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA Correspondence to: Shu-Wing Ng, e-mail: sng@partners.org Keywords: ovarian cancer, tumorigenesis, RNA metabolism, cell adhesion, RNA sequencing Received: October 21, 2015 Accepted: January 24, 2016 Published: February 08, 2016 ABSTRACT 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. |
| Databáze: | OpenAIRE |
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