METTL3 Promotes Cutaneous T-Cell Lymphoma Progression by Regulating ARHGEF12 Expression

Int J Mol Sci. 2025 Apr 11;26(8):3640. doi: 10.3390/ijms26083640.

Abstract

Recent studies have identified N6-methyladenosine (m6A) RNA methylation as a key regulatory mechanism in tumor progression. This study aimed to elucidate the biological function and clinical relevance of the m6A methyltransferase METTL3 in cutaneous T-cell lymphoma (CTCL). Our findings demonstrated that METTL3 expression is upregulated in CTCL, and its knockdown suppresses CTCL progression. Mechanistically, the downregulation of METTL3-mediated m6A modification on ARHGEF12 mRNA accelerated its degradation, a process that is closely associated with tumor behaviors. These results suggest that METTL3 may serve as a potential therapeutic target in CTCL.

Keywords: ARHGEF12; METTL3; m6A.

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine / metabolism
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lymphoma, T-Cell, Cutaneous* / genetics
  • Lymphoma, T-Cell, Cutaneous* / metabolism
  • Lymphoma, T-Cell, Cutaneous* / pathology
  • Male
  • Methyltransferases* / genetics
  • Methyltransferases* / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rho Guanine Nucleotide Exchange Factors* / genetics
  • Rho Guanine Nucleotide Exchange Factors* / metabolism
  • Skin Neoplasms* / genetics
  • Skin Neoplasms* / metabolism
  • Skin Neoplasms* / pathology

Substances

  • Methyltransferases
  • METTL3 protein, human
  • Rho Guanine Nucleotide Exchange Factors
  • Adenosine
  • N-methyladenosine
  • RNA, Messenger