miR-17-5p 靶向 p300/CBP 相关因子，调节培养的前列腺癌细胞中的雄激素受体转录活性。
miR-17-5p targets the p300/CBP-associated factor and modulates androgen receptor transcriptional activity in cultured prostate cancer cells.
机构信息
Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68178, USA.
出版信息
BMC Cancer. 2012 Oct 24;12:492. doi: 10.1186/1471-2407-12-492.
BACKGROUND
Androgen 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.
METHODS
Expression 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.
RESULTS
PCAF 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.
CONCLUSIONS
PCAF 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.
背景
雄激素受体（AR）信号对于前列腺癌（PCa）的发生和发展至关重要。AR 的转录活性涉及共激活因子（包括 p300/CBP 相关因子（PCAF））的染色质募集。在疾病的发展和进展过程中，已经在 PCa 细胞中鉴定出不同的 miRNA 表达谱。miRNA 是否调节 PCa 细胞中的 PCAF 表达以调节 AR 转录活性尚不清楚。
方法
通过 qRT-PCR、Western blot 和免疫细胞化学研究了几种 PCa 细胞系中 PCAF 的表达。通过染色质免疫沉淀、报告基因构建分析和 MTS 测定确定 PCAF 表达对 PCa 细胞中 AR 调节的转录活性和细胞生长的影响。使用荧光素酶报告基因测定评估 miR-17-5p 对 PCAF 的靶向作用。
结果
在几种 PCa 细胞系中 PCAF 上调。PCAF 的上调促进了培养的 PCa 细胞中 AR 的转录激活和细胞生长。PCa 细胞中 PCAF 的表达与 miR-17-5p 的下调相关。miR-17-5p 靶向 PCAF mRNA 的 3'-非翻译区导致翻译抑制和 RNA 降解，从而调节 PCa 细胞中的 AR 转录活性。
结论
在培养的 PCa 细胞中 PCAF 上调，而 PCAF 的上调与 miR-17-5p 的下调相关。miR-17-5p 靶向 PCAF 调节培养的 PCa 细胞中的 AR 转录活性和细胞生长。
Zotero 插件