Oncotarget

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This article has been corrected. Correction in: Oncotarget. 2017; 8(7):12533.

Pinin interacts with C-terminal binding proteins for RNA alternative splicing and epithelial cell identity of human ovarian cancer cells

Yanli Zhang _, Jamie Sui-Lam Kwok, Pui-Wah Choi, Minghua Liu, Junzheng Yang, Margit Singh, Shu-Kay Ng, William R. Welch, Michael G. Muto, Stephen KW Tsui, Stephen P. Sugrue, Ross S. Berkowitz and Shu-Wing Ng

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Oncotarget. 2016; 7:11397-11411. https://doi.org/10.18632/oncotarget.7242

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Abstract

Yanli Zhang1, Jamie Sui-Lam Kwok2, Pui-Wah Choi1, Minghua Liu2, Junzheng Yang1, Margit Singh1, Shu-Kay Ng4, William R. Welch5, Michael G. Muto1, Stephen KW Tsui2, Stephen P. Sugrue3, Ross S. Berkowitz1, Shu-Wing Ng1

1Laboratory of Gynecologic Oncology, Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, MA, USA

2School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong

3Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, FL, USA

4School of Medicine and Menzies Health Institute Queensland, Griffith University, Meadowbrook, Australia

5Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

Correspondence to:

Shu-Wing Ng, e-mail: [email protected]

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.


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