Xie Jianjun, Chen Xiumei, Wang Weiwan, Guan Zhenghui, Hou Jianquan, Lin Jianzhong
Department of Urology, The First Affiliated Hospital of Soochow University, China.
Department of Urology, The Affiliated Suzhou Hospital Hospital of Nanjing Medical, University, China.
J Cancer. 2022 Apr 4;13(7):2138-2149. doi: 10.7150/jca.65329. eCollection 2022.
Docetaxel resistance seriously affects its clinical application in prostate cancer (PCa). Long noncoding RNAs (lncRNAs) influence the chemosensitivity of various cancers. However, the potential involvement of lncRNAs in docetaxel sensitivity remains largely unknown in PCa. In the present study, we used RNA sequencing to compare the expression profiles of lncRNAs in docetaxel-resistant PCa cells and their parental cells and identified a novel lncRNA, ENSG00000234147, termed as PCa docetaxel resistance-associated lncRNA1 (PCDRlnc1). Our results indicated that PCDRlnc1 is closely associated with docetaxel resistance in PCa, and PCDRlnc1 knockout markedly sensitized the resistant cells to docetaxel and . In addition, PCDRlnc1 inhibition markedly suppressed docetaxel-induced autophagy. Conversely, PCDRlnc1 overexpression promoted autophagy. Mechanistically, PCDRlnc1 interacted with UHRF1 (ubiquitin-like with plant homeodomain and ring finger domains 1) and promoted its transcription level in PCa cells, leading to the activation of autophagic Beclin-1 signaling. Together, our data demonstrate that PCDRlnc1 is a novel key regulator of PCa docetaxel resistance, suggesting that it may be used as a potential biomarker of docetaxel resistance and therapeutic target in PCa.
多西他赛耐药严重影响其在前列腺癌（PCa）中的临床应用。长链非编码RNA（lncRNAs）影响多种癌症的化疗敏感性。然而，lncRNAs在多西他赛敏感性中的潜在作用在PCa中仍 largely未知。在本研究中，我们使用RNA测序比较了多西他赛耐药PCa细胞及其亲本细胞中lncRNAs的表达谱，并鉴定出一种新型lncRNA，ENSG00000234147，命名为前列腺癌多西他赛耐药相关lncRNA1（PCDRlnc1）。我们的结果表明，PCDRlnc1与PCa中的多西他赛耐药密切相关，PCDRlnc1敲除显著使耐药细胞对多西他赛敏感。此外，PCDRlnc1抑制显著抑制多西他赛诱导的自噬。相反，PCDRlnc1过表达促进自噬。机制上，PCDRlnc1与UHRF1（具有植物同源结构域和环指结构域的泛素样蛋白1）相互作用并促进其在PCa细胞中的转录水平，导致自噬性Beclin-1信号的激活。总之，我们的数据表明PCDRlnc1是PCa多西他赛耐药的一种新型关键调节因子，表明它可能用作多西他赛耐药的潜在生物标志物和PCa的治疗靶点。
