Related Experiment Video

Updated: Jan 15, 2026

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
10:44

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

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Epigenetic regulation of Cereblon in cancer: molecular mechanisms and clinical implications

Joo Mi Yi1,2

  • 1Department of Microbiology and Immunology, College of Medicine, Inje University, Busan, 47392, South Korea. jmyi76@inje.ac.kr.

Genes & Genomics
|October 15, 2025
PubMed
Abstract

Insights

Promoter methylation epigenetically silences Cereblon (CRBN) in various cancers, leading to poor prognosis and resistance to immunomodulatory drugs (IMiDs). Restoring CRBN expression via epigenetic therapies may improve cancer treatment outcomes.

Area of Science:

  • Cancer Biology
  • Epigenetics
  • Pharmacogenomics

Background:

  • Cereblon (CRBN) is crucial for CRL4-CRBN E3 ubiquitin ligase complex function and a key target of immunomodulatory drugs (IMiDs) in cancer therapy.
  • Reduced CRBN expression correlates with poor IMiD response and treatment resistance, indicating non-genetic regulatory mechanisms.
  • Investigating CRBN's epigenetic regulation is vital for understanding cancer treatment resistance.

Purpose of the Study:

  • To analyze CRBN expression patterns across diverse cancer types.
  • To investigate the role of promoter methylation in regulating CRBN expression.
  • To assess the clinical significance of CRBN methylation and expression as prognostic biomarkers.

Main Methods:

  • CRBN expression analyzed using the GENT2 database.
  • CRBN methylation status assessed in cancer cell lines via methylation-specific PCR (MSP) and bisulfite sequencing.
  • Clinical significance evaluated using TCGA and GENT2 databases with Kaplan-Meier survival analyses.

Main Results:

  • CRBN expression was significantly downregulated in breast, cervical, head and neck, lung, and skin cancers.
  • CRBN promoter hypermethylation correlated with increased mortality risk in breast, lung, acute myeloid leukemia, and bladder cancers.
  • Combined low CRBN expression and high promoter methylation strongly predicted poor outcomes in breast and lung cancers.

Conclusions:

  • CRBN expression is epigenetically regulated by promoter methylation in specific cancers, contributing to treatment resistance and poor prognosis.
  • CRBN methylation and expression are significant pan-cancer prognostic biomarkers.
  • Epigenetic therapies hold potential for restoring CRBN function and overcoming therapeutic resistance.
Keywords:
Cancer biomarkersCereblon (CRBN)DNA methylationE3 Ubiquitin LigaseEpigenetic regulation

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