MiR-1271 Inhibits Cell Growth in Prostate Cancer by Targeting ERG

Abstract

ETS-related gene (ERG) is an oncogene that is commonly found in prostate cancer (PCa). Several miRNAs have been reported to be associated with PCa. This study was undertaken to identify miRNAs that act as a tumor suppressor by targeting ERG. We collected 70 PCa and paired adjacent non-tumor (Adjacent-N) tissues and analyzed ERG expression by immunohistochemistry(IHC). Expression of 6 miRNAs (miR-21,-34a,-96,-125b,-150 and miR-1271) was analyzed by qRT-PCR. Luciferase reporter assay was performed to examine miRNA binding to the 3′-UTR of target genes. The effects of ectopic expression of miRNA on cell growth and MAPK signaling pathway were investigated in in PC-3 and LNCaP cell lines. Among 70 PCa cases, 13 (18.6%) were ERG positive. No significant difference of miR-34a, 96, 125b, and 150 expression was found between PCa and Adjacent-N tissues. Significantly higher level of miR-21 and lower level of miR-1271 expression were found in cancer tissues. Furthermore, miR-1271 was down-regulated in ERG-positive PCa cases (p < 0.05). Based on luciferase reporter assay, we identified ERG gene as a direct target gene for miR-1271. Transfection of a miR-1271 mimics into PC-3 and LNCaP cells repressed the ERG expression and significantly suppressed cell growth. Lastly, ectopic expression of miR-1271 inhibits AKT1, p38gama and CREB kinase activity. Our results suggested that reduced expression of miR-1271 may be involved in the ERG expression and that miR-1271 could be a therapeutic target for ERG-positive prostate cancer patients.

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