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The RNA-binding protein hnRNPA2 regulates ?-catenin protein expression and is
overexpressed in prostate cancer
#MMPMID24823909
Stockley J
; Villasevil ME
; Nixon C
; Ahmad I
; Leung HY
; Rajan P
RNA Biol
2014[]; 11
(6
): 755-65
PMID24823909
show ga
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-?RGG 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 ?-catenin (CTNNB1). Both wild-type hnRNPA2 and
hnRNPA2-?RGG act on CTNNB1 3'-UTR mRNA, increasing endogenous CTNNB1 mRNA
expression and ?-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 ?-catenin expression and other cancer-relevant
genes.
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