J Cancer 2022; 13(7):2138-2149. doi:10.7150/jca.65329 This issue
1. Department of Urology, The First Affiliated Hospital of Soochow University, China.
2. Department of Urology, The Affiliated Suzhou Hospital Hospital of Nanjing Medical, University, China.
3. Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, China.
4. Central Laboratory, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing, Medical University, China.
5. Department of Urology, Taizhou Clinical Medical School of Nanjing Medical University, China.
*These authors contributed equally to this work.
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 in vitro and in vivo. 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.
Keywords: LncRNA, Prostate cancer, Chemoresistance, Autophagy, UHRF1