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Updated: Sep 11, 2025

SUMO-Binding Entities SUBEs as Tools for the Enrichment, Isolation, Identification, and Characterization of the SUMO Proteome in Liver Cancer
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USP8 deubiquitylation-boosted NSUN4 potentiates lung squamous cell carcinoma progression by m5C methylation of DHCR24

Yang Jiang1, Pengyuan Zhu1, Zhenchuan Liu1

  • 1Department of Thoracic Surgery, Tongji Hospital, School of Medicine, Tongji University, Xincun Road 389, Shanghai 200065, P.R. China.

Cell Reports
|August 15, 2025
PubMed

Insights

Overexpression of NSUN4 promotes lung squamous cell carcinoma (LUSC) by regulating oncogene methylation. USP8 stabilizes NSUN4, impacting LUSC progression and patient survival.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • RNA methylation, specifically 5-methylcytosine (m5C), plays roles in cellular processes.
  • The function of RNA methyltransferase NSUN4 in lung squamous cell carcinoma (LUSC) is not well understood.

Purpose of the Study:

  • To investigate the biological roles of NSUN4 in LUSC.
  • To elucidate the mechanism of NSUN4-mediated m5C modification in LUSC pathogenesis.

Main Methods:

  • Overexpression and knockdown of NSUN4 in LUSC models.
  • Ubiquitin-specific peptidase 8 (USP8) interaction and stabilization assays.
  • High-throughput RNA bisulfite sequencing.
  • Analysis of NSUN4 and DHCR24 expression in clinical LUSC samples.

Main Results:

  • NSUN4 overexpression exhibits oncogenic effects in LUSC.
  • USP8 stabilizes NSUN4 via inhibition of polyubiquitination.
  • NSUN4 and YBX1 target m5C methylation sites in DHCR24's 3' UTR, driving LUSC.
  • High NSUN4 and DHCR24 expression correlates with poor patient survival.

Conclusions:

  • NSUN4 acts as an oncogene in LUSC, stabilized by USP8.
  • NSUN4-mediated m5C methylation of DHCR24 is a key mechanism in LUSC development.
  • NSUN4 and DHCR24 are potential prognostic biomarkers and therapeutic targets for LUSC.
Keywords:
5-methylcytosineCP: CancerCP: Molecular biologycancer proliferationdeubiquitylationlung squamous cell carcinoma

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