2. Academic Validation
  3. circCYP24A1 promotes Docetaxel resistance in prostate Cancer by Upregulating ALDH1A3

circCYP24A1 promotes Docetaxel resistance in prostate Cancer by Upregulating ALDH1A3

  • Biomark Res. 2022 Jul 13;10(1):48. doi: 10.1186/s40364-022-00393-1.
Haoli Yin  # 1 2,  Haixiang Qin  # 1 2,  Lei Yang  # 3 4,  Mengxia Chen 1 2,  Yang Yang 1 2,  Wenlong Zhang 1 2,  Jiange Hao 5,  Qun Lu 1 2,  Jingyan Shi 1 2,  Junlong Zhuang 1 2,  Xuefeng Qiu 6 7,  Hongqian Guo 8 9
Affiliations

Affiliations

  • 1 Department of Urology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, China.
  • 2 Institute of Urology, Nanjing University, Nanjing, China.
  • 3 Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, 210093, Jiangsu, China.
  • 4 Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, 210093, Jiangsu, China.
  • 5 Department of Urology, The Second Affiliated Hospital of Dalian Medical University, Dalian, 116000, China.
  • 6 Department of Urology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, China. [email protected].
  • 7 Institute of Urology, Nanjing University, Nanjing, China. [email protected].
  • 8 Department of Urology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, China. [email protected].
  • 9 Institute of Urology, Nanjing University, Nanjing, China. [email protected].
  • # Contributed equally.
PMID: 35831872 DOI: 10.1186/s40364-022-00393-1
Abstract

Background: Docetaxel (DTX) is the most widely prescribed first-line chemotherapy for advanced prostate Cancer (PCa). Unfortunately, DTX resistance invariably emerges, leading to worse prognosis of PCa. Growing evidence has shown that circRNAs had complex spatiotemporal specificity during the tumor development and oncogenesis. This study was designed to investigate the biological functions and possible molecular mechanisms of circRNAs in DTX resistance of PCa.

Methods: circRNAs in established DTX-resistant DU145 cell line were identified by RNA sequencing. Biological function of circCYP24A1 was verified in vitro and in vivo. The potential role of circCYP24A1 in the development of DTX-resistant PCa was investigated via dual-luciferase reporter assays, RIP assays and RNA pull-down assays. Univariate and multivariate logistic regression analyses was used to predict DTX-chemotherapy response based on patients' clinical and biological information.

Results: CircCYP24A1 was identified to be upregulated in DTX-resistant DU145 cells. Upregulated circCYP24A1 was found to suppress the DTX chemosensitivity in vitro and in vivo. Furthermore, we found that circCYP24A1 promoted DTX resistance in PCa via regulating ALDH1A3 expression by sponging miR-1301-3p and activating PI3K/Akt/mTOR signaling pathway. Statistical analyses elucidated that circCYP24A1 was an independent risk factor to predict DTX response (OR = 0.165; 95% CI: 0.038-0.723; P = 0.017).

Conclusions: This study demonstrated that circCYP24A played an essential role in DTX resistance in PCa, suggesting that circCYP24A1 could be a promising biomarker to predict DTX response and a potential therapeutic target in PCa patients resistant to DTX chemotherapy.

Keywords

ALDH1A3; Docetaxel resistance; Prostate cancer; circCYP24A1; miR-1301-3p.

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