miR-331-3p regulates ERBB-2 expression and androgen receptor signaling in prostate cancer.
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.
Epis
Michael R
MR
Laboratory for Cancer Medicine, University of Western Australia Center for Medical Research, Western Australian Institute for Medical Research, Perth, Western Australia 6000, Australia.
Giles
Keith M
KM
Barker
Andrew
A
Kendrick
Tulene S
TS
Leedman
Peter J
PJ
D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism* / Q000502:physiology; D008954:Models, Biological; D008969:Molecular Sequence Data; D011471:Prostatic Neoplasms / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism*; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction
D020413:3' Untranslated Regions; D035683:MicroRNAs; D018719:Erb-b2 Receptor Tyrosine Kinases; D011944:Receptors, Androgen; C544460:MIRN331 microRNA, human