The RNA-binding Protein HuR Opposes the Repression of ERBB-2 Gene Expression by MicroRNA miR-331-3p in Prostate Cancer Cells

ERBB-2 overexpression is associated with the development and progression of cancer and mediates its resistance to therapy. It has been suggested that post-transcriptional mechanisms control the overexpression of ERBB-2 in prostate cancer (PCa). We recently demonstrated that the 3′-untranslated region (3′-UTR) of ERBB-2 mRNA contains two specific target sites for binding of the microRNA miR-331-3p and that miR-331-3p represses ERBB-2 expression and signaling in PCa cells. Here we investigate a U-rich element situated in close proximity to the distal miR-331-3p target site in the ERBB-2 3′-UTR. Specific binding of HuR to this U-rich element promotes ERBB-2 expression in PCa cells. We show that HuR antagonizes the repressive action of miR-331-3p on its distal ERBB-2 3′-UTR target site. These results support a model in which the interplay between RNA-binding proteins and microRNAs controls the post-transcriptional regulation of gene expression and suggest that both HuR and miR-331-3p participate in the overexpression of ERBB-2 observed in some PCas. Background: The combined effect of HuR and miR-331-3p on ERBB-2 expression in prostate cancer (PCa) is unknown. Results: HuR regulated ERBB-2 expression and antagonized the repressive action of miR-331-3p. Conclusion: HuR and miR-331-3p participate in overexpression of ERBB-2 in PCa. Significance: Interplay between HuR and miR-331-3p regulates the post-transcriptional expression of ERBB-2 in PCa.