Related Experiment Video

Updated: May 13, 2025

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
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Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel

Published on: September 8, 2017

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N6-methyladenosine-modified circQKI inhibits prostate cancer docetaxel-sensitivity via miR-188-3p/Beclin-1 pathway

Tong Zhao1, Kai Li1, Yetao Zhang1

  • 1Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Life Sciences
|April 18, 2025
PubMed
Abstract

Insights

Circular RNA circQKI promotes docetaxel resistance in prostate cancer by activating autophagy. Targeting circQKI or autophagy may overcome resistance, offering new therapeutic strategies for castration-resistant prostate cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Docetaxel (DTX) is a first-line treatment for advanced castration-resistant prostate cancer (CRPC).
  • Drug resistance, particularly to DTX, remains a significant clinical challenge in CRPC management.
  • Circular RNAs (circRNAs) have emerged as key regulators in the development of drug resistance.

Purpose of the Study:

  • To investigate the role and mechanism of a novel circRNA, circQKI, in mediating DTX resistance in CRPC.
  • To elucidate the regulatory network involving circQKI, microRNA-188-3p (miR-188-3p), and autophagy in CRPC.
  • To explore the upstream regulation of circQKI expression through m6A modification.

Main Methods:

  • Establishment of DTX-resistant prostate cancer cell lines (PC3/DR, 22RV1/DR).
  • Manipulation of circQKI expression using siRNA and overexpression plasmids.
  • Assessment of cell viability, apoptosis, and colony formation.
  • Verification of circQKI-miR-188-3p interaction using dual-luciferase reporter, RIP, and RNA pull-down assays.
  • Analysis of autophagy activation via Western blot and transmission electron microscopy (TEM).
  • Evaluation of in vivo drug resistance using subcutaneous xenograft models.
  • Investigation of m6A modification using m6A RIP-PCR and knockdown of METTL3/IGF2BP2.

Main Results:

  • CircQKI expression was significantly upregulated in DTX-resistant cells.
  • CircQKI overexpression enhanced DTX resistance by sponging miR-188-3p, leading to increased Beclin-1 expression and autophagy activation.
  • Inhibition of Beclin-1 or treatment with chloroquine partially restored DTX sensitivity.
  • METTL3-mediated N6-methyladenosine (m6A) modification stabilized circQKI via IGF2BP2, causing its accumulation in resistant cells.
  • In vivo studies confirmed that circQKI overexpression reduced tumor sensitivity to DTX by promoting autophagy.

Conclusions:

  • CircQKI drives DTX resistance in CRPC through the miR-188-3p/Beclin-1 axis and subsequent autophagy activation.
  • CircQKI expression is regulated by METTL3-dependent m6A modification and IGF2BP2.
  • Targeting circQKI or autophagy pathways presents a promising therapeutic strategy to overcome DTX resistance in prostate cancer.
Keywords:
AutophagyDocetaxel resistanceM6AProstate cancercircQKImiR-188-3p

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