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, Professor Imran and Leung, Professor Hing and Nixon, Mr Colin and Rajan, Dr Prabhakar and Stockley, Dr Jacqueline and Martin, Miss Eugenia |
| 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 > School of Cancer Sciences College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary 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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