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UHRF1 as an epigenetic therapeutic target in Cancer

Chun Yang1, Zhitao Yin1, Hexue Yuan1

  • 1Department of Colorectal Surgery, Shenyang Coloproctology Hospital, Shenyang, 110002, Liaoning, China.

Molecular Biology Reports
|March 3, 2026
PubMed

Insights

UHRF1, an epigenetic regulator overexpressed in cancers, drives tumor growth and resistance. Targeting UHRF1 specifically offers a new therapeutic strategy with reduced toxicity for next-generation cancer treatments.

Area of Science:

  • Epigenetics
  • Cancer Biology
  • Molecular Oncology

Background:

  • UHRF1 (ubiquitin-like with PHD and RING finger domains 1) is a key epigenetic regulator.
  • Overexpression of UHRF1 is linked to diverse cancers, promoting tumor progression and therapy resistance.
  • UHRF1 integrates DNA methylation, histone modification, and ubiquitin signaling.

Purpose of the Study:

  • To explore UHRF1 as a druggable target for cancer therapy.
  • To investigate domain-specific targeting strategies for UHRF1.
  • To review potential therapeutic approaches and synergistic combinations for UHRF1 inhibition.

Main Methods:

  • Review of existing literature on UHRF1 function and therapeutic targeting.
  • Analysis of natural compounds and synthetic inhibitors targeting UHRF1.
  • Exploration of UHRF1 inhibition in combination with other cancer therapies.

Main Results:

  • UHRF1 overexpression silences tumor suppressors and stabilizes oncoproteins.
  • Domain-specific UHRF1 inhibition presents a refined therapeutic window with reduced toxicity.
  • Various agents, including natural compounds and synthetic inhibitors, show potential in disrupting UHRF1.
  • UHRF1 inhibition may synergize with DNMT/HDAC inhibitors, immunotherapy, and ferroptosis inducers.

Conclusions:

  • UHRF1 is a promising biomarker and druggable target for epigenetic cancer therapies.
  • Targeting UHRF1 offers a precise strategy distinct from global epigenetic modification.
  • Further research into UHRF1-targeted therapies holds significant potential for next-generation cancer treatment.
Keywords:
BiomarkerCancer therapyDNA methylationEpigenetic regulationFerroptosisImmune regulationSmall molecule inhibitorsUHRF1

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