miR-17-5p targets the p300/CBP-associated factor and modulates androgen receptor transcriptional activity in cultured prostate cancer cells

Abstract

BackgroundAndrogen receptor (AR) signalling is critical to the initiation and progression of prostate cancer (PCa). Transcriptional activity of AR involves chromatin recruitment of co-activators, including the p300/CBP-associated factor (PCAF). Distinct miRNA expression profiles have been identified in PCa cells during the development and progression of the disease. Whether miRNAs regulate PCAF expression in PCa cells to regulate AR transcriptional activity is still unclear.MethodsExpression of PCAF was investigated in several PCa cell lines by qRT-PCR, Western blot, and immunocytochemistry. The effects of PCAF expression on AR-regulated transcriptional activity and cell growth in PCa cells were determined by chromatin immunoprecipitation, reporter gene construct analysis, and MTS assay. Targeting of PCAF by miR-17-5p was evaluated using the luciferase reporter assay.ResultsPCAF was upregulated in several PCa cell lines. Upregulation of PCAF promoted AR transcriptional activation and cell growth in cultured PCa cells. Expression of PCAF in PCa cells was associated with the downregulation of miR-17-5p. Targeting of the 3’-untranslated region of PCAF mRNA by miR-17-5p caused translational suppression and RNA degradation, and, consequently, modulation of AR transcriptional activity in PCa cells.ConclusionsPCAF is upregulated in cultured PCa cells, and upregulation of PCAF is associated with the downregulation of miR-17-5p. Targeting of PCAF by miR-17-5p modulates AR transcriptional activity and cell growth in cultured PCa cells.

The other face of miR-17-92a cluster, exhibiting tumor suppressor effects in prostate cancer

“…It can be speculated that the enhanced sensitivity of the miR-17-92a cluster expressing LNCaP 104-S cells to CDX is mediated through interfering androgen receptor function, as miR-17-5p has been shown to inhibit androgen receptor transcriptional activity through targeting p300/CBP [23]. The improved sensitivity of PC-3 cells expressing miR-17-92a cluster to DTX and VX680 in combination is presumably mediated through the inhibition of LIMK1 expression and activity (Figure 2 and Figure 3).…”

Microdissecting the role of microRNAs in the pathogenesis of prostate cancer

“…Another miRNA that modulates the expression of AR is miR-17-5p by directly repressing the expression of p300/CBP-associated factor, a co-activator of AR (90). Other miRNAs that are hypothesized to play an important role in the process of PCa metastasization include miR-100 and miR-218.…”

Screening Biomarkers of Prostate Cancer by Integrating microRNA and mRNA Microarrays

“…PCAF is upregulated in cultured PC cells, and upregulation of PCAF is associated with the downregulation of miR-17-5p (Gong et al, 2012). The regulation of Livin expression may involve miR-198 in prostate cancer cell lines (Ye et al, 2013).…”