The RNA-binding protein hnRNPA2 regulates β-catenin protein expression and is overexpressed in prostate cancer

Stockley, J., Villasevil, M. E. M., Nixon, C., Ahmad, I. , Leung, H. and Rajan, P. (2014) The RNA-binding protein hnRNPA2 regulates β-catenin protein expression and is overexpressed in prostate cancer. RNA Biology, 11(6), pp. 755-765. (doi:10.4161/rna.28800) (PMID:24823909) (PMCID:PMC4156506)

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Abstract

The RNA-binding protein hnRNPA2 (HNRNPA2B1) is upregulated in cancer, where it controls alternative pre-mRNA splicing of cancer-relevant genes. Cytoplasmic hnRNPA2 is reported in aggressive cancers, but is functionally uncharacterized. We explored the role of hnRNPA2 in prostate cancer (PCa). Methods: hnRNPA2 function/localization/expression in PCa was determined using biochemical approaches (colony forming/proliferation/luciferase reporter assays/flow cytometry/immunohistocytochemistry). Binding of hnRNPA2 within cancer-relevant 3′-UTR mRNAs was identified by bioinformatics. Results: RNAi-mediated knockdown of hnRNPA2 reduced colony forming and proliferation, while hnRNPA2 overexpression increased proliferation of PCa cells. Nuclear hnRNPA2 is overexpressed in high-grade clinical PCa, and is also observed in the cytoplasm in some cases. Ectopic expression of a predominantly cytoplasmic variant hnRNPA2-ΔRGG also increased PCa cell proliferation, suggesting that cytoplasmic hnRNPA2 may also be functionally relevant in PCa. Consistent with its known cytoplasmic roles, hnRNPA2 was associated with 3′-UTR mRNAs of several cancer-relevant mRNAs including β-catenin (CTNNB1). Both wild-type hnRNPA2 and hnRNPA2-ΔRGG act on CTNNB1 3′-UTR mRNA, increasing endogenous CTNNB1 mRNA expression and β-catenin protein expression and nuclear localization. Conclusion: Nuclear and cytoplasmic hnRNPA2 are present in PCa and appear to be functionally important. Cytoplasmic hnRNPA2 may affect the cancer cell phenotype through 3′-UTR mRNA-mediated regulation of β-catenin expression and other cancer-relevant genes.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Ahmad, Dr Imran and Martin, Miss Eugenia and Leung, Professor Hing and Nixon, Mr Colin and Rajan, Dr Prabhakar and Stockley, Dr Jacqueline
Authors: Stockley, J., Villasevil, M. E. M., Nixon, C., Ahmad, I., Leung, H., and Rajan, P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
Journal Name:RNA Biology
Publisher:Landes Bioscience
ISSN:1547-6286
ISSN (Online):1555-8584
Published Online:24 April 2014
Copyright Holders:Copyright © 2014 The Authors
First Published:First published in RNA Biology 11(6):755-765
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
595221Systems analysis of RNA-binding protein function in metastic prostate cancer.Prabhakar RajanCancer Research UK (CAN-RES-UK)C19198/A15339ICS - CLINICAL TRIALS RESEARCH