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

Jing Xiao, Ai Yu Gong, Alex N. Eischeid, Dongqing Chen, Caishu Deng, Charles Y F Young, Xian-Ming Chen

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1514-1522
Number of pages9
JournalProstate
Volume72
Issue number14
DOIs
StatePublished - Oct 1 2012

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Androgen Receptors
Human Activities
Prostatic Neoplasms
Down-Regulation
Up-Regulation
Cell Line
Co-Repressor Proteins
RNA Stability
Chemoprevention
3' Untranslated Regions
nuclear receptor subfamily 0, group B, member 2
MicroRNAs
Vegetables
Prostate
Carcinogenesis
Epithelial Cells
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Urology
  • Oncology

Cite this

MiR-141 modulates androgen receptor transcriptional activity in human prostate cancer cells through targeting the small heterodimer partner protein. / Xiao, Jing; Gong, Ai Yu; Eischeid, Alex N.; Chen, Dongqing; Deng, Caishu; Young, Charles Y F; Chen, Xian-Ming.

In: Prostate, Vol. 72, No. 14, 01.10.2012, p. 1514-1522.

Research output: Contribution to journalArticle

Xiao, Jing ; Gong, Ai Yu ; Eischeid, Alex N. ; Chen, Dongqing ; Deng, Caishu ; Young, Charles Y F ; Chen, Xian-Ming. / MiR-141 modulates androgen receptor transcriptional activity in human prostate cancer cells through targeting the small heterodimer partner protein. In: Prostate. 2012 ; Vol. 72, No. 14. pp. 1514-1522.
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abstract = "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.",
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AB - 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.

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