HOTAIR 是一种 REST 调节的 lncRNA，可促进去势抵抗性前列腺癌的神经内分泌分化。
HOTAIR is a REST-regulated lncRNA that promotes neuroendocrine differentiation in castration resistant prostate cancer.
机构信息
Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan; Department of Urology, School of Medicine, Shu-Tien Urological Research Center, National Yang-Ming University, Taipei, Taiwan; Department of Urology, Taipei Veterans General Hospital, Taipei, Taiwan.
出版信息
Cancer Lett. 2018 Oct 1;433:43-52. doi: 10.1016/j.canlet.2018.06.029. Epub 2018 Jun 23.
Long non-coding RNAs (lncRNAs) are emerging as novel diagnostic markers of prostate cancer (PCa) and new determinants of castration-resistant PCa (CRPC), an aggressive and metastatic form of PCa. In addition to androgen receptor (AR) signaling, neuroendocrine differentiation (NED) is associated with CRPC. Recent reports demonstrate that the downregulation of repressor element-1 silencing transcription factor (REST) protein is a key step in NED of PCa cells. Here, we report HOTAIR as a novel REST-repressed lncRNA that is upregulated in NED PCa cells and in CRPC. HOTAIR overexpression is sufficient to induce, whereas knockdown of HOTAIR suppressed NED of PCa cells. Gene ontology (GO) analysis of differentially expressed genes under HOTAIR overexpression and in CRPC versus benign prostatic hyperplasia (BPH) suggests that HOTAIR may participate in PCa progression. Taken together, our results provide the first evidence of lncRNA HOTAIR as a driver for NED of PCa cells.
长非编码 RNA（lncRNAs）正在成为前列腺癌（PCa）的新型诊断标志物和去势抵抗性前列腺癌（CRPC）的新决定因素，CRPC 是一种侵袭性和转移性的 PCa 形式。除了雄激素受体（AR）信号外，神经内分泌分化（NED）也与 CRPC 有关。最近的报告表明，抑制元件 1 沉默转录因子（REST）蛋白的下调是 PCa 细胞发生 NED 的关键步骤。在这里，我们报告 HOTAIR 是一种新型的 REST 抑制的 lncRNA，在 NED PCa 细胞和 CRPC 中上调。HOTAIR 的过表达足以诱导，而 HOTAIR 的敲低则抑制了 PCa 细胞的 NED。HOTAIR 过表达和 CRPC 与良性前列腺增生（BPH）相比差异表达基因的基因本体（GO）分析表明，HOTAIR 可能参与了 PCa 的进展。总之，我们的研究结果首次提供了 lncRNA HOTAIR 作为 PCa 细胞 NED 驱动因子的证据。
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