Related Experiment Video

Updated: Sep 14, 2025

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
04:01

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics

Published on: March 15, 2024

1.2K

ZNF207-driven PRDX1 lactylation and NRF2 activation in regorafenib resistance and ferroptosis evasion

Tianfeng Yang1, Suyu Zhang1, Kun Nie1

  • 1School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, PR China; State Key Laboratory of Shaanxi for Natural Medicines Research and Engineering, Xi'an 710061, PR China.

Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
|July 18, 2025
PubMed

Insights

Zinc Finger Protein 207 (ZNF207) drives resistance to Regorafenib (RGF) in liver cancer by inhibiting ferroptosis. Targeting the ZNF207-PRDX1-NRF2 pathway restores RGF sensitivity and offers new therapeutic strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Regorafenib (RGF) is a key second-line treatment for advanced hepatocellular carcinoma (HCC).
  • Drug resistance, particularly to RGF, significantly limits treatment efficacy and patient outcomes in HCC.
  • Understanding the molecular mechanisms of RGF resistance is crucial for developing effective therapeutic strategies.

Purpose of the Study:

  • To identify key molecular drivers of RGF resistance in HCC.
  • To elucidate the mechanism by which ZNF207 confers RGF resistance.
  • To explore the therapeutic potential of targeting the identified resistance pathway.

Main Methods:

  • CRISPR/Cas9 screening was employed in RGF-treated HCC cells to identify resistance-associated genes.
  • Western blotting and immunoprecipitation were used to analyze protein modifications and interactions.
  • Cell viability assays, ferroptosis assays, and knockdown/inhibition experiments were performed to assess functional roles.

Main Results:

  • CRISPR/Cas9 screening identified Zinc Finger Protein 207 (ZNF207) as a critical mediator of RGF resistance.
  • ZNF207 promotes RGF resistance by enhancing the lactylation of peroxiredoxin 1 (PRDX1), leading to NRF2 activation and suppressed ferroptosis.
  • Knockdown of ZNF207 or disruption of the ZNF207-PRDX1-NRF2 pathway restored RGF sensitivity by reactivating ferroptosis.

Conclusions:

  • The ZNF207-PRDX1-NRF2 signaling axis is a novel mechanism driving RGF resistance in HCC.
  • Targeting protein lactylation and ferroptosis suppression presents a promising strategy to overcome RGF resistance.
  • This pathway may represent a broader therapeutic target for overcoming drug resistance in other cancers.
Keywords:
FerroptosisHepatocellular carcinomaPRDX1 lactylationRegorefenib resistanceZNF207

More Related Videos

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists10:51

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Published on: November 15, 2013

12.9K
Ferritinophagy: Assessing the Selective Degradation of Iron by Autophagy in Human Fibroblasts09:21

Ferritinophagy: Assessing the Selective Degradation of Iron by Autophagy in Human Fibroblasts

Published on: February 23, 2024

1.0K

Related Concept Videos

NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
7.9K
Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
1.6K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.6K
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.4K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K