Oncotarget

Research Papers:

Regulation and functional significance of CDC42 alternative splicing in ovarian cancer

Xiaolong He _, Chengfu Yuan and Jilai Yang

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Oncotarget. 2015; 6:29651-29663. https://doi.org/10.18632/oncotarget.4865

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Abstract

Xiaolong He1, Chengfu Yuan2, Jilai Yang1

1Department of Biopharmaceutical Sciences, College of Pharmacy-Rockford, The University of Illinois at Chicago, Rockford, IL 61107, USA

2Medical College of China Three Gorges University, Yichang, Hubei, 443002, People’s Republic of China

Correspondence to:

Xiaolong He, e-mail: xiaohe@uic.edu

Keywords: alternative splicing, PTBP1, CDC42, ovarian cancer

Received: November 20, 2014     Accepted: August 12, 2015     Published: August 22, 2015

ABSTRACT

Our previous study found that splicing factor polypyrimidine tract-binding protein 1 (PTBP1) had a role in tumorigenesis but the underlying mechanism remained unclear. In this study, we observed that knockdown of PTBP1 inhibited filopodia formation. Subsequently, we found that PTBP1 regulated the alternative splicing of CDC42, a major regulator of filopodia formation. Two CDC42 variants, CDC42-v1 and CDC42-v2, can be generated through alternative splicing. Knockdown of PTBP1 increased the expression of CDC42-v2. Ectopic expression of individual variants showed that CDC42-v2 suppressed filopodia formation, opposite to the effect of CDC42-v1. Quantitative RT-PCR revealed that CDC42-v2 was expressed at lower levels in ovarian cancer cell lines and ovarian tumor tissues than in normal control cells and tissues. Further, CDC42-v2 was observed to have inhibitory effects on ovarian tumor cell growth, colony formation in soft agar and invasiveness. In contrast, these inhibitory effects were not found with CDC42-v1. Taken together, above results suggest that the role of PTBP1 in tumorigenesis may be partly mediated by its regulation of CDC42 alternative splicing and CDC42-v2 might function as a tumor suppressor.


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