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Acetylation of interferon regulatory factor-5 suppresses androgen receptor and downregulates expression of Sox2

Hilal Acidereli1,2, Fatma Aysun Turut1, Ozge Cevik3

  • 1Department of Biochemistry, Faculty of Pharmacy, Cumhuriyet University, Sivas, Turkey.

Cell Biochemistry and Function
|March 29, 2021
PubMed

Insights

Interferon regulatory factor-5 (IRF5) acts as a tumor suppressor in prostate cancer. Its expression is linked to androgen receptor signaling and stem cell factors, with lower levels correlating to advanced disease stages.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Interferon regulatory factor-5 (IRF5) is a transcription factor with tumor suppressor functions.
  • IRF5's role in prostate cancer and its regulatory mechanisms are not well understood.
  • Dysregulated IRF5 protein function is observed in various human cancers.

Purpose of the Study:

  • To investigate the role and regulatory mechanisms of IRF5 in prostate cancer.
  • To explore the interaction between IRF5, androgen receptor (AR) signaling, and stem cell factors in prostate cancer.
  • To determine the potential of IRF5 as a therapeutic target for prostate cancer.

Main Methods:

  • Utilized human prostate cancer cell lines (PC3, DU145, LNCaP) and clinical samples.
  • Employed immunofluorescence staining, co-immunoprecipitation, and ChIP assays to assess protein interactions.
  • Performed luciferase assays to analyze target gene regulation by IRF5, AR, and other factors.

Main Results:

  • IRF5 expression is significantly lower in androgen-dependent prostate cancer cells and tissues.
  • IRF5 expression is down-regulated in advanced stages of prostate tumors, indicating a pathological role.
  • IRF5 interacts with AR signaling and stem cell factors (Nanog, Oct4, Sox2), influencing AR acetylation and cellular signaling pathways.

Conclusions:

  • IRF5 plays a crucial role in prostate cancer, acting as a tumor suppressor.
  • IRF5 expression is regulated by AR signaling and stem cell factors in prostate cancer.
  • IRF5 represents a promising therapeutic target for androgen-dependent prostate cancers.
Keywords:
IRF5Sox2androgen receptorprostate cancerstem cell factor

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