miR-331-3p Regulates ERBB-2 Expression and Androgen Receptor Signaling in Prostate Cancer

Michael Epis, Keith Giles, Andrew Barker, T.S. Kendrick, Peter Leedman

Research output: Contribution to journalArticle

125 Citations (Scopus)

Abstract

MicroRNAs (miRNAs) are short, non-coding RNAs that regulate gene expression and are aberrantly expressed in human cancer. The ERBB-2 tyrosine kinase receptor is frequently overexpressed in prostate cancer and is associated with disease progression and poor survival. We have identified two specific miR-331-3p target sites within the ERBB-2 mRNA 3′-untranslated region and show that miR-331-3p expression is decreased in prostate cancer tissue relative to normal adjacent prostate tissue. Transfection of multiple prostate cancer cell lines with miR-331-3p reduced ERBB-2 mRNA and protein expression and blocked downstream phosphatidylinositol 3-kinase/AKT signaling. Furthermore, miR-331-3p transfection blocked the androgen receptor signaling pathway in prostate cancer cells, reducing activity of an androgen-stimulated prostate-specific antigen promoter and blocking prostate-specific antigen expression. Our findings provide insight into the regulation of ERBB-2 expression in cancer and suggest that miR-331-3p has the capacity to regulate signaling pathways critical to the development and progression of prostate cancer cells.
Original languageEnglish
Pages (from-to)24696-24704
JournalThe Journal of Biological Chemistry
Volume284
Issue number37
DOIs
Publication statusPublished - 2009

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