Lgr4 promotes prostate tumorigenesis through the Jmjd2a/AR signaling pathway

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Leucine-rich repeat domain containing G protein-coupled receptor 4 (Lgr4) is involved in cancer progression through histone demethylase regulation.
• The specific molecular mechanisms of Lgr4 in prostate cancer (PCa) progression, particularly its interaction with histone demethylases, remain largely unexplored.

Purpose of the Study:

• To investigate the molecular mechanism of Lgr4 in prostate cancer (PCa) progression.
• To explore the relationship between Lgr4, Jmjd2a, and the androgen receptor (AR) signaling pathway in PCa.

Main Methods:

• Overexpression of Lgr4 in PCa cell lines (LNCaP and PC-3) via pcDNA3.1(+)/Lgr4 plasmid transfection.
• Assessment of Jmjd2a mRNA expression, cell apoptosis, cell cycle, AR levels, and interactions using techniques like co-immunoprecipitation and luciferase reporter assays.
• Silencing of Jmjd2a and PSA to evaluate their roles in Lgr4-mediated effects.

Main Results:

• Lgr4 overexpression increased Jmjd2a mRNA expression, reduced apoptosis, and caused S-phase cell cycle arrest in PCa cells.
• These effects were reversed by Jmjd2a silencing.
• Lgr4 overexpression enhanced AR levels and its interaction with Jmjd2a.
• Lgr4 promoted AR interaction with the PSA promoter, and PSA silencing mitigated Lgr4-induced apoptosis reduction and cell cycle arrest.

Conclusions:

• Lgr4 activates the Jmjd2a/AR signaling pathway in prostate cancer.
• This activation promotes AR interaction with the PSA promoter, leading to decreased PCa cell apoptosis and cell cycle arrest.
• Lgr4 may serve as a novel tumor marker for PCa, offering new insights into its progression.