MiR-125b regulation of androgen receptor signaling via modulation of the receptor complex co-repressor NCOR2

Xiaoping Yang, Lynne T Bemis, Lih Jen Su, Dexiang Gao, Thomas W. Flaig

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Recognition of micro-RNA function and their contribution to the biology of disease has given a new insight into disease mechanisms, with these discoveries potentially improving clinical diagnostic and therapeutic options. miR-125b has been identified as an important regulator in various cancers, including prostate cancer, but the mechanism of this regulation remains incompletely understood. In these studies, the effect of castration on miR-125b serum expression was evaluated in mice, simulating androgen deprivation. Furthermore, miR-125b expression was measured by quantitative real-time polymerase chain reaction (qRT-PCR) in LNCaP prostate cancer cells treated with the antiandrogen bicalutamide. Using LNCaP cells, the effect of miR-125b modulation on apoptotic protein and NCOR2, a co-repressor of androgen receptor (AR), was examined by Western blot. A 3¢-untranslated region (UTR) luciferase-binding assay was performed to confirm that miR-125b targets NCOR2. We found that surgical castration induced an initial increase in the expression of circulating miR-125b in mice, while sham surgery did not. In addition, AR blockade via bicalutamide was associated with the rapid release of miR-125b into the cell culture medium of prostate cancer cells. A previously studied target of miR-125b, a regulator in the apoptotic pathway, BAK1, could not completely account for the role of miR-125b in prostate cancer. Thus, we looked for additional targets of miR-125b and found that NCOR2, which is a repressor of AR, is a direct target of miR-125b. We found that NCOR2 protein expression was blocked by mimics of miR-125b, and a luciferase-binding assay confirmed that NCOR2 is a direct target of miR-125b. Our data provide novel evidence that miR-125b is an important regulator of the AR with specific ramification for the effectiveness of antiandrogens and other hormonal therapies in prostate cancer.

Original languageEnglish (US)
Pages (from-to)55-62
Number of pages8
JournalBioResearch Open Access
Volume1
Issue number2
DOIs
StatePublished - Jan 1 2012
Externally publishedYes

Fingerprint

Co-Repressor Proteins
Androgen Receptors
Prostatic Neoplasms
Modulation
Androgen Antagonists
Luciferases
Assays
Castration
Cells
Polymerase chain reaction
3' Untranslated Regions
MicroRNAs
Cell culture
Surgery
Androgens
Culture Media
Proteins
Real-Time Polymerase Chain Reaction
Cell Culture Techniques
Western Blotting

Keywords

  • Androgen receptor complex
  • Apoptosis
  • Castration
  • Circulating micro-RNA
  • Prostate cancer

Cite this

MiR-125b regulation of androgen receptor signaling via modulation of the receptor complex co-repressor NCOR2. / Yang, Xiaoping; Bemis, Lynne T; Su, Lih Jen; Gao, Dexiang; Flaig, Thomas W.

In: BioResearch Open Access, Vol. 1, No. 2, 01.01.2012, p. 55-62.

Research output: Contribution to journalArticle

Yang, Xiaoping ; Bemis, Lynne T ; Su, Lih Jen ; Gao, Dexiang ; Flaig, Thomas W. / MiR-125b regulation of androgen receptor signaling via modulation of the receptor complex co-repressor NCOR2. In: BioResearch Open Access. 2012 ; Vol. 1, No. 2. pp. 55-62.
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