M6A reader YTHDF1 promotes malignant progression of laryngeal squamous carcinoma through activating the EMT pathway by EIF4A3

Cell Signal. 2024 Feb:114:111002. doi: 10.1016/j.cellsig.2023.111002. Epub 2023 Dec 2.

Abstract

Laryngeal squamous cell carcinoma (LSCC) is one of the common malignant tumors in the head and neck region, and its high migration and invasion seriously threaten the survival and health of patients. In cancer development, m6A RNA modification plays a crucial role in regulating gene expression and signaling. This study delved into the function and mechanism of the m6A reading protein YTHDF1 in LSCC. It was found that YTHDF1 was highly expressed in the GEO database and LSCC tissues. Cell function experiments confirmed that the downregulation of YTHDF1 significantly inhibited the proliferation, migration, and invasion ability of LSCC cells. Further studies revealed that EIF4A3 was a downstream target gene of YTHDF1, and knockdown of EIF4A3 similarly significantly inhibited the malignant progression of LSCC in both in vivo and in vitro experiments. The molecular mechanism studies suggested that YTHDF1-EIF4A3 may promote the malignant development of LSCC by activating the EMT signaling pathway. This study provides important clues for an in-depth understanding of the pathogenesis of LSCC and is a solid foundation for the discovery of new therapeutic targets and approaches.

Keywords: EIF4A3; EMT; Laryngeal squamous cell carcinoma; YTHDF1; m6A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Squamous Cell* / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • DEAD-box RNA Helicases / metabolism
  • Eukaryotic Initiation Factor-4A / genetics
  • Eukaryotic Initiation Factor-4A / metabolism
  • Gene Expression Regulation, Neoplastic
  • Head and Neck Neoplasms*
  • Humans
  • Laryngeal Neoplasms* / genetics
  • Laryngeal Neoplasms* / metabolism
  • MicroRNAs* / metabolism
  • RNA-Binding Proteins / metabolism
  • Squamous Cell Carcinoma of Head and Neck

Substances

  • 6-methyladenine
  • MicroRNAs
  • EIF4A3 protein, human
  • Eukaryotic Initiation Factor-4A
  • DEAD-box RNA Helicases
  • YTHDF1 protein, human
  • RNA-Binding Proteins