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

• Published in: RNA biology Vol. 11; no. 6; pp. 755 - 765
• Main Authors: Stockley, Jacqueline, Villasevil, M Eugenia M, Nixon, Colin, Ahmad, Imran, Leung, Hing Y, Rajan, Prabhakar
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.06.2014; Landes Bioscience
• Subjects: 3' Untranslated Regions; 3-UTR mRNA; beta Catenin - genetics; Cell Line, Tumor; Cell Proliferation; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; CTNNB1; Cytoplasm - metabolism; Gene Expression Regulation, Neoplastic; Heterogeneous-Nuclear Ribonucleoprotein Group A-B - metabolism; HNRNPA2B1; Humans; Male; Neoplasm Grading; prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Protein Transport; Research Paper; RNA, Messenger - metabolism; β-catenin; β-catenin; CTNNB1; prostate cancer; 3-UTR mRNA; HNRNPA2B1
• ISSN: 1547-6286; 1555-8584
• DOI: 10.4161/rna.28800

Introduction 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.