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NSUN2 promotes osteosarcoma metastasis via stabilizing UBE2S mRNA in an m5C-dependent manner

Yu Chen1, Ranran Sun2, Liwen Liu2

  • 1Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China; Department of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.

Cellular Signalling
|August 17, 2025
PubMed

Insights

NSUN2, an RNA methyltransferase, promotes osteosarcoma metastasis by stabilizing UBE2S mRNA. This NSUN2-UBE2S axis enhances the UBE2S/β-catenin pathway, indicating a potential therapeutic target for osteosarcoma progression.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • 5-methylcytosine (m5C) is a key RNA modification involved in cancer.
  • NSUN2 is the main enzyme catalyzing m5C formation.
  • The role of NSUN2 in osteosarcoma remains largely unknown.

Purpose of the Study:

  • To investigate the role and mechanism of NSUN2 in osteosarcoma.
  • To identify downstream targets and pathways regulated by NSUN2.
  • To explore the clinical significance of NSUN2 in osteosarcoma.

Main Methods:

  • Analysis of NSUN2 expression in osteosarcoma tissues and cell lines.
  • Functional assays to assess the impact of NSUN2 on metastasis and EMT.
  • RNA sequencing and expression correlation to identify NSUN2 targets.
  • Western blotting and ubiquitination assays to study protein interactions.

Main Results:

  • NSUN2 expression is upregulated in osteosarcoma and correlates with poor prognosis.
  • NSUN2 promotes osteosarcoma cell metastasis and epithelial-mesenchymal transition (EMT).
  • UBE2S is a downstream target of NSUN2, with NSUN2 stabilizing UBE2S mRNA via m5C modification.
  • UBE2S interacts with and ubiquitinates β-catenin, enhancing its stability and activation.
  • Dual-high expression of NSUN2 and UBE2S predicts shorter survival in osteosarcoma patients.

Conclusions:

  • NSUN2 promotes osteosarcoma metastasis through the UBE2S/β-catenin signaling pathway.
  • Targeting the NSUN2-UBE2S axis may offer a therapeutic strategy for osteosarcoma.
Keywords:
5-methylcytosineMetastasisNSUN2OsteosarcomaUBE2S

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