miR-141 modulates androgen receptor transcriptional activity in human prostate cancer cells through targeting the small heterodimer partner protein.
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.
Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, Nebraska 68178, USA.
Jing
J
Xiao
Ai-Yu
AY
Gong
Alex N
AN
Eischeid
Dongqing
D
Chen
Caishu
C
Deng
Charles Y F
CY
Young
Xian-Ming
XM
Chen
D015153:Blotting, Western; D045744:Cell Line, Tumor; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012313:RNA / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation
C410798:AR protein, human; D017879:Isothiocyanates; C533895:MIRN141 microRNA, human; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D011944:Receptors, Androgen; D018160:Receptors, Cytoplasmic and Nuclear; C099713:nuclear receptor subfamily 0, group B, member 2; D012313:RNA; C058305:phenethyl isothiocyanate