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FTO facilitates colorectal cancer chemoresistance via regulation of NUPR1-dependent iron homeostasis

  • 0Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, China.
Redox Biology +

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May 7, 2025

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May 7, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Drug resistance in colorectal cancer (CRC) is a major challenge. Our study identifies the FTO-NUPR1 axis as key to chemoresistance, offering a new therapeutic target for overcoming drug resistance in CRC.

Area Of Science

  • Oncology
  • Molecular Biology
  • Epigenetics

Background

  • Colorectal cancer (CRC) drug resistance is a primary cause of mortality.
  • N6-methyladenosine (m6A) modification is a key regulator in cancer, but its role in CRC chemoresistance is unclear.

Purpose Of The Study

  • To identify m6A regulators driving CRC progression and chemoresistance.
  • To elucidate the mechanism by which these regulators impact CRC chemoresistance.

Main Methods

  • Correlation analysis of m6A regulatory gene expression profiles in CRC.
  • CRISPR/Cas9-mediated genome engineering to create knockout cellular and mouse models.
  • Mechanistic studies on mRNA stabilization and degradation pathways.

Main Results

  • FTO (N6-methyladenosine demethylase) was identified as a key regulator of CRC chemoresistance.
  • FTO stabilizes NUPR1 mRNA by targeting an m6A site, preventing degradation.
  • Simultaneous targeting of FTO and NUPR1 enhanced chemotherapy efficacy in CRC cells.

Conclusions

  • The FTO-NUPR1 axis is a critical determinant in colorectal cancer pathobiology and chemoresistance.
  • Modulating the m6A methylome, specifically targeting FTO and NUPR1, holds potential for overcoming CRC chemoresistance.

Keywords:

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