The androgen receptor (AR) plays an important role in the progression of prostate cancer and is the most important therapeutic target. However, androgen deprivation therapy will finally lead patients to progress to castration-resistant prostate cancer (CRPC). Here, we confirmed that GAS5, a long noncoding RNA, could interact and suppress AR transactivation in CRPC C4-2 cells. Knockdown GAS5 by short hairpin RNA would enhance the transcription of AR via promote AR recruitment to the promoter of its downstream target genes. Functionally, GAS5 overexpression inhibits cell proliferation partially through inhibiting AR transactivation in C4-2 cells. Moreover, knocking down GAS5 protects C4-2 cells from the docetaxel-induced cell apoptosis. In return, the suppressed AR was found to downregulate the GAS5 expression, which forms a feedback loop resulted in AR high transcription activity in CRPC. Collectively, our findings revealed the important role of GAS5 in AR axis activity regulation and CRPC progression. Targeting GAS5 to intervene the feedback loop might be a new potential therapeutic approach for the patients at CRPC stage.

中文翻译：

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长链非编码 RNA GAS5 相互作用并抑制前列腺癌细胞中的雄激素受体活性

雄激素受体（AR）在前列腺癌的进展中起重要作用，是最重要的治疗靶点。然而，雄激素剥夺疗法最终将导致患者进展为去势抵抗性前列腺癌 (CRPC)。在这里，我们证实 GAS5，一种长链非编码 RNA，可以相互作用并抑制 CRPC C4-2 细胞中的 AR 反式激活。通过短发夹 RNA 敲低 GAS5 将通过促进 AR 募集到其下游靶基因的启动子来增强 AR 的转录。在功能上，GAS5 过表达通过抑制 C4-2 细胞中的 AR 反式激活来部分抑制细胞增殖。此外，敲除 GAS5 可保护 C4-2 细胞免受多西紫杉醇诱导的细胞凋亡。作为回报，抑制的 AR 被发现下调 GAS5 的表达，形成反馈回路导致 CRPC 中的 AR 高转录活性。总的来说，我们的研究结果揭示了 GAS5 在 AR 轴活动调节和 CRPC 进展中的重要作用。针对 GAS5 干预反馈回路可能是 CRPC 阶段患者的一种新的潜在治疗方法。