miR-141 modulates androgen receptor transcriptional activity in human prostate cancer cells through targeting the small heterodimer partner protein

• Published in: The Prostate Vol. 72; no. 14; pp. 1514 - 1522
• Main Authors: Xiao, Jing, Gong, Ai-Yu, Eischeid, Alex N., Chen, Dongqing, Deng, Caishu, Young, Charles Y.F., Chen, Xian-Ming
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-10-2012
• Subjects: androgen receptor; Blotting, Western; Cell Line, Tumor; Down-Regulation; Gene Expression Regulation, Neoplastic; Humans; Isothiocyanates - pharmacology; Male; microRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miR-141; Oligonucleotides, Antisense - genetics; Oligonucleotides, Antisense - pharmacology; PEITC; prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Real-Time Polymerase Chain Reaction; Receptors, Androgen - genetics; Receptors, Androgen - metabolism; Receptors, Cytoplasmic and Nuclear - biosynthesis; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Cytoplasmic and Nuclear - metabolism; RNA - genetics; RNA - metabolism; Shp; Transcription, Genetic; Up-Regulation
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.22501

BACKGROUND
Aberrant expressions of microRNAs, including upregulation of miR‐141, are closely associated with the tumorigenesis of prostate cancer (PCa). The orphan receptor small heterodimer partner (Shp) is a co‐repressor to androgen receptor (AR) and represses AR‐regulated transcriptional activity.
METHODS
Here, we investigated the correlation of Shp expression with the cellular level of miR‐141 and its effects on AR transcriptional activity in non‐malignant and malignant human prostate epithelial cell lines.
RESULTS
We found that Shp was downregulated in multiple PCa cell lines. The mature form of miR‐141 was upregulated in PCa cells. miR‐141 could target 3′‐untranslated region of Shp mRNA resulting in translational suppression and RNA degradation. Moreover, enforced expression of Shp or inhibition of miR‐141 function by anti‐miR‐141 attenuated AR‐regulated transcriptional activity in AR‐responsive LNCaP cells. Phenethyl isothiocyanate, a natural constituent of many edible cruciferous vegetables, increased Shp expression, downregulated miR‐141, and inhibited AR transcriptional activity in LNCaP cells.
CONCLUSIONS
Shp is a target for miR‐141 and it is downregulated in cultured human PCa cells with the involvement of upregulation of miR‐141, which promotes AR transcriptional activity. Moreover, Shp and miR‐141 could be targets for chemoprevention for PCa. Prostate 72:1514–1522, 2012. © 2012 Wiley Periodicals, Inc.