Long non-coding RNA PCDRlnc1 confers docetaxel resistance in prostate cancer by promoting autophagy

Jianjun Xie1,2, Xiumei Chen3, Weiwan Wang4

  • 1Department of Urology, The First Affiliated Hospital of Soochow University, China.

Journal of Cancer
|May 6, 2022
PubMed

Insights

A novel long noncoding RNA, PCDRlnc1, drives docetaxel resistance in prostate cancer (PCa) by promoting autophagy. Inhibiting PCDRlnc1 sensitizes PCa cells to docetaxel, offering a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Docetaxel resistance is a major challenge in prostate cancer (PCa) treatment.
  • Long noncoding RNAs (lncRNAs) are implicated in cancer chemosensitivity, but their role in PCa docetaxel resistance is unclear.

Purpose of the Study:

  • To identify novel lncRNAs involved in docetaxel resistance in prostate cancer.
  • To investigate the functional role and mechanism of a newly identified lncRNA, PCDRlnc1, in PCa docetaxel resistance.

Main Methods:

  • RNA sequencing was employed to compare lncRNA expression profiles in docetaxel-resistant and parental PCa cells.
  • In vitro and in vivo experiments assessed the effects of PCDRlnc1 knockout and overexpression on docetaxel sensitivity and autophagy.
  • Mechanistic studies explored the interaction between PCDRlnc1, UHRF1, and Beclin-1 signaling.

Main Results:

  • A novel lncRNA, PCDRlnc1 (ENSG00000234147), was identified and found to be upregulated in docetaxel-resistant PCa cells.
  • PCDRlnc1 knockout sensitized PCa cells to docetaxel both in vitro and in vivo.
  • PCDRlnc1 inhibition suppressed docetaxel-induced autophagy, while overexpression promoted it, mediated by interaction with UHRF1 and activation of Beclin-1 signaling.

Conclusions:

  • PCDRlnc1 is a key regulator of docetaxel resistance in prostate cancer.
  • PCDRlnc1 may serve as a potential biomarker for docetaxel resistance and a therapeutic target in PCa treatment.

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