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Roles and mechanisms of NSUN2-mediated RNA m5C modification in cancer progression and immune modulation

Chunhong Li1, Yixiao Yuan2, Xiulin Jiang2

  • 1Department of Oncology, Suining Central Hospital, Suining, Sichuan, China.

Frontiers in Immunology
|November 19, 2025
PubMed

Insights

The RNA methyltransferase NSUN2 (NOP2/Sun RNA methyltransferase 2) drives cancer progression and immune evasion by regulating gene expression and the tumor microenvironment. Targeting NSUN2 offers potential for novel cancer therapies.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Immunology

Background:

  • RNA epigenetic modifications, particularly 5-methylcytosine (m5C), are crucial for gene expression regulation in cancer.
  • NSUN2 (NOP2/Sun RNA methyltransferase 2) is a key enzyme responsible for m5C modification across various RNA species.

Purpose of the Study:

  • To review the multifaceted roles of NSUN2 in cancer progression, including its impact on cellular functions and the tumor immune microenvironment.
  • To discuss the clinical implications of NSUN2 as a biomarker and therapeutic target in oncology.

Main Methods:

  • Literature review of studies investigating NSUN2 function in cancer.
  • Analysis of NSUN2's molecular mechanisms in RNA modification, stability, processing, export, and translation.
  • Examination of NSUN2's influence on tumor-associated pathways and the tumor immune microenvironment.

Main Results:

  • NSUN2 promotes tumorigenesis by enhancing cell proliferation, drug resistance, epithelial-mesenchymal transition, and metabolic reprogramming.
  • Dysregulated NSUN2 expression correlates with poor patient prognosis and suggests its utility as a biomarker.
  • NSUN2 significantly modulates the tumor immune microenvironment by affecting immune checkpoint molecules, cytokines, and immune cell functions, leading to immune evasion.

Conclusions:

  • NSUN2 plays a critical role in both cancer cell-intrinsic processes and the modulation of anti-tumor immunity.
  • Understanding NSUN2's mechanisms provides a foundation for developing targeted cancer therapies and improving immunotherapy strategies.
  • Further research into NSUN2 is warranted to fully explore its therapeutic potential in oncology.
Keywords:
5-methylcytosine (m5C)NSUN2RNA epigenetic modificationcancer progressionimmune evasiontumor immune regulationtumor microenvironment

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