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NSUN2/m5C/TPI1 axis promotes glycolysis and immune evasion in breast cancer

Xinming Song1, Qihang Li1, Ziteng Xiao1

  • 1Department of Head and Neck Oncology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China.

Journal of Translational Medicine
|June 6, 2026
PubMed
Abstract

Insights

The methyltransferase NSUN2 promotes breast cancer (BC) progression by enhancing glycolysis and immune evasion. NSUN2 stabilizes TPI1 via m5C modification, increasing PD-L1 expression and tumor growth.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Aerobic glycolysis and immune evasion are key drivers of tumor development.
  • 5-methylcytosine (m5C) methyltransferase NSUN2 functions as an oncogene in breast cancer (BC).
  • The precise molecular mechanisms of NSUN2 in BC progression require further investigation.

Purpose of the Study:

  • To investigate the role of NSUN2 in breast cancer (BC) progression.
  • To elucidate the underlying molecular mechanisms by which NSUN2 influences BC.
  • To explore the interplay between NSUN2, YBX1, and TPI1 in BC.

Main Methods:

  • In vitro assays assessed cell proliferation, glycolysis, and immune evasion.
  • Tumor growth was evaluated in a mouse model.
  • RNA immunoprecipitation, m5C RNA immunoprecipitation, and dual-luciferase reporter assays examined molecular interactions.

Main Results:

  • NSUN2 and TPI1 were upregulated in BC cells; NSUN2 knockdown inhibited proliferation, glycolysis, and immune evasion.
  • NSUN2 enhanced TPI1 stability through m5C modification, a process recognized by YBX1.
  • TPI1 overexpression reversed the inhibitory effects of NSUN2 silencing on tumor growth and immune cell infiltration in vivo.

Conclusions:

  • NSUN2 accelerates BC progression by promoting glycolysis and immune evasion.
  • NSUN2 facilitates TPI1 m5C methylation in a YBX1-dependent manner, increasing PD-L1 expression and immune evasion.
  • NSUN2 represents a potential therapeutic target for breast cancer.
Keywords:
Breast cancerGlycolysisImmune evasionM5C methylationNSUN2PD-L1TPI1

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