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


CONCLUSIONS
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.
Institute of Cancer Sciences; College of Medical, Veterinary, and Life Sciences; University of Glasgow; Cancer Research UK Beatson Institute; Bearsden, UK.
Jacqueline
J
Stockley
Institute of Cancer Sciences; College of Medical, Veterinary, and Life Sciences; University of Glasgow; Cancer Research UK Beatson Institute; Bearsden, UK.
M Eugenia M
ME
Villasevil
Cancer Research UK Beatson Institute; The Beatson Institute for Cancer Research; Bearsden, UK.
Colin
C
Nixon
Institute of Cancer Sciences; College of Medical, Veterinary, and Life Sciences; University of Glasgow; Cancer Research UK Beatson Institute; Bearsden, UK.
Imran
I
Ahmad
Institute of Cancer Sciences; College of Medical, Veterinary, and Life Sciences; University of Glasgow; Cancer Research UK Beatson Institute; Bearsden, UK; Cancer Research UK Beatson Institute; The Beatson Institute for Cancer Research; Bearsden, UK.
Hing Y
HY
Leung
Institute of Cancer Sciences; College of Medical, Veterinary, and Life Sciences; University of Glasgow; Cancer Research UK Beatson Institute; Bearsden, UK.
Prabhakar
P
Rajan
D020413:3' Untranslated Regions; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000378:metabolism*; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D021381:Protein Transport; D012333:RNA, Messenger / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics*
D020413:3' Untranslated Regions; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D012333:RNA, Messenger; D051176:beta Catenin; C439768:hnRNP A2
3-UTR mRNA; CTNNB1; HNRNPA2B1; prostate cancer; β-catenin