Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China.
Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China.
Mol Cell Probes. 2020 Oct;53:101607. doi: 10.1016/j.mcp.2020.101607. Epub 2020 May 26.
Androgen receptor (AR) and long non-coding RNAs (lncRNA) play important roles in the initiation and progression of prostate cancer (PCa). The present study was designed to investigate whether lncRNA growth arrest-specific 5 (GAS5) is involved in the regulation of dexamethasone on the proliferation of AR PCa and AR PCa cell lines.
Cell proliferation and cell cycle distribution were assessed using MTT assay and flow cytometry, respectively. GAS5 expression was examined by quantitative real-time PCR. AR protein level was examined by Western blot. RNA immunoprecipitation and RNA pull-down were performed to analyze the binding of GAS5 to AR.
In AR PCa cell line PC3, dexamethasone upregulated GAS5 expression, induced cell cycle arrest in the G0/G1 phase and inhibited cell proliferation, which were enhanced by GAS5 overexpression and attenuated by GAS5 silencing. However, in AR PCa cell line 22Rv1, dexamethasone had no obvious effects on GAS5 expression, cell cycle distribution and cell proliferation. AR was localized in the cytoplasm and bound to GAS5, counteracting the proliferation-inhibitory effect of GAS5.
Taken together, GAS5 participates in the regulation of dexamethasone on the proliferation of AR PCa and AR PCa cell lines.
雄激素受体（AR）和长链非编码 RNA（lncRNA）在前列腺癌（PCa）的发生和发展中起重要作用。本研究旨在探讨长链非编码 RNA 生长停滞特异性基因 5（GAS5）是否参与调节地塞米松对 AR PCa 和 AR PCa 细胞系增殖的影响。
分别采用 MTT 法和流式细胞术检测细胞增殖和细胞周期分布。采用实时定量 PCR 检测 GAS5 表达。采用 Western blot 检测 AR 蛋白水平。采用 RNA 免疫沉淀和 RNA 下拉实验分析 GAS5 与 AR 的结合。
在 AR PCa 细胞系 PC3 中，地塞米松上调 GAS5 表达，诱导细胞周期停滞在 G0/G1 期，并抑制细胞增殖，这些作用可被 GAS5 过表达增强，也可被 GAS5 沉默减弱。然而，在 AR PCa 细胞系 22Rv1 中，地塞米松对地塞米松对 GAS5 表达、细胞周期分布和细胞增殖没有明显影响。AR 定位于细胞质中并与 GAS5 结合，抵消了 GAS5 的增殖抑制作用。
综上所述，GAS5 参与调节地塞米松对 AR PCa 和 AR PCa 细胞系增殖的影响。
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