JMJD2A participates in cytoskeletal remodeling to regulate castration-resistant prostate cancer docetaxel resistance

Xiang Cai1, Xi Duan2, Tielong Tang1

  • 1Department of Urology, Affiliated Hospital of North Sichuan Medical College, No. 1 Maoyuan South Road, Sichuan, 637000, Nanchong, China.

BMC Cancer
|May 10, 2023
PubMed
Abstract

Insights

JMJD2A promotes docetaxel resistance in prostate cancer by altering cytoskeleton remodeling via the miR-34a/STMN1/β3-Tubulin pathway, impacting cell proliferation and apoptosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Castration-resistant prostate cancer (CRPC) often develops resistance to docetaxel chemotherapy.
  • The underlying mechanisms of docetaxel resistance, particularly involving cytoskeleton remodeling, require further investigation.

Purpose of the Study:

  • To elucidate the role of JMJD2A in regulating cytoskeleton remodeling in docetaxel-resistant CRPC.
  • To identify the molecular pathway, including microRNA and protein interactions, through which JMJD2A exerts its effects.

Main Methods:

  • Analysis of JMJD2A, miR-34a, and cytoskeleton-related protein expression in CRPC patient tissues.
  • In vitro studies involving knockdown of JMJD2A, STMN1, and TUBB3 in CRPC cell lines.
  • Assessment of cell viability, apoptosis, and molecular interactions using qPCR, western blot, dual-luciferase reporter, and co-immunoprecipitation assays.

Main Results:

  • Higher JMJD2A and STMN1 expression, with lower miR-34a and β3-Tubulin, observed in docetaxel-resistant CRPC.
  • JMJD2A regulates cytoskeletal remodeling via the miR-34a/STMN1/β3-Tubulin axis.
  • miR-34a overexpression led to decreased STMN1, increased β3-Tubulin, microtubule disruption, reduced proliferation, G0/G1 cell cycle arrest, and enhanced apoptosis.

Conclusions:

  • JMJD2A promotes docetaxel resistance in prostate cancer.
  • The miR-34a/STMN1/β3-Tubulin axis is a key mediator of JMJD2A-induced cytoskeleton remodeling and chemoresistance.
  • Targeting JMJD2A or modulating this axis may offer therapeutic strategies for overcoming docetaxel resistance in CRPC.

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