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

Tulene S. Kendrick,Michael R. Epis,Peter J. Leedman,Keith M. Giles,Andrew Barker

doi:10.1074/jbc.m109.030098

Tulene S. Kendrick, Michael R. Epis + Show 3 more

Open Access

https://doi.org/10.1074/jbc.m109.030098

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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.

Highlights

Prostate cancer (PCa)3 is the second leading cause of cancer death among men in the United States
We show that miR-331-3p directly regulates ERBB-2 mRNA and protein expression in multiple PCa cell lines via two specific ERBB-2 3Ј-untranslated regions (3Ј-UTRs) target binding sites
Sion by qRT-PCR, reverse transcription and PCR were carried out 3Ј-UTR the Tarusing TaqMan miRNA assay kits (Applied Biosystems) for hsa- getScan context score for each site was significantly lower than miR-331, U44 small nuclear RNA (part for both of the miR-331-3p sites (70 and 27, 42 and 54, and 35 number 4373384), and U6 small nuclear RNA

Summary

Introduction

Prostate cancer (PCa)3 is the second leading cause of cancer death among men in the United States. Compared with a negative control miRNA precursor, miR-331-3p significantly down-regulated expression of both ERBB-2 protein and RNA in each of the PCa cell lines, independent of AR status (Fig. 2, A and B).

Results

Conclusion