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Updated: Jan 9, 2026

Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer
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Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer

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Multi-omics analysis reveals that ALYREF-mediated m5C modification promotes platinum resistance in ovarian cancer via

Shimin Yang1,2, Pengyuan He2, Wei Wang2,3

  • 1Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing, China.

Cell Death & Disease
|December 4, 2025
PubMed

Insights

Platinum resistance in ovarian cancer is linked to RNA modification. The study identifies ALYREF as a key regulator, showing the NSUN2/ALYREF/LGR4 pathway drives resistance by stabilizing LGR4 mRNA and activating Wnt signaling.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Platinum resistance is a significant challenge in ovarian cancer treatment.
  • The role of 5-methylcytosine (m5C) RNA modification in chemoresistance is emerging but not fully understood in this context.

Purpose of the Study:

  • To elucidate the functional role of m5C RNA modification and its associated proteins in platinum resistance in ovarian cancer.
  • To identify key molecular regulators driving platinum resistance.

Main Methods:

  • Integrated analysis of RNA-Seq and single-cell transcriptomic data from cisplatin-resistant ovarian cancer cells and patient samples.
  • Functional studies involving knockdown, overexpression, and mutant constructs of ALYREF and NSUN2.
  • Multi-omics analyses including RNA-Seq, m5C-BIS-Seq, and RIP-Seq.

Main Results:

  • The m5C reader protein ALYREF was identified as a key regulator of platinum resistance.
  • ALYREF binds to m5C-modified LGR4 mRNA, increasing its stability.
  • This interaction activates the Wnt/β-catenin signaling pathway, a mechanism dependent on NSUN2-mediated m5C modification of LGR4 mRNA.

Conclusions:

  • The NSUN2/ALYREF/LGR4 axis drives platinum resistance in ovarian cancer via m5C-dependent LGR4 mRNA stabilization and Wnt signaling activation.
  • Targeting ALYREF presents a potential therapeutic strategy to overcome platinum resistance in ovarian cancer.

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