Mechanism of METTL14 and m6A modification of lncRNA MALAT1 in the proliferation of oral squamous cell carcinoma cells

Oral Dis. 2023 Jul;29(5):2012-2026. doi: 10.1111/odi.14220. Epub 2022 May 17.


Objectives: Methyltransferase-like 14 (METTL14) plays an epigenetic role in various cancer through N6-methyladenosine (m6A) modification. This study sought to analyze the mechanism of METTL14 in oral squamous cell carcinoma (OSCC) cell proliferation.

Methods: Expression levels of METTL14, lncRNA metastasis associated with lung adenocarcinoma transcript 1 (lncRNA MALAT1), microRNA (miR)-224-5p, and histone lysine demethylase 2A (KDM2A) in OSCC tissues (N = 40), and cell lines (FaDu, SCC-25, CAL-27, and SCC-15) were detected. Cell viability and colony formation capacity were assessed. m6A level, stability, and subcellular localization of lncRNA MALAT1 were determined. Nude mouse xenograft tumor assay was performed to confirm the role of METTL14 in vivo.

Results: METTL14 and lncRNA MALAT1 were upregulated, and miR-224-5p was downregulated in OSCC tissues and cells. Silencing METTL14 repressed OSCC cell viability and colony formation. Overexpression of MALAT1 and KDM2A or miR-224-5p downregulation reversed the inhibition of silencing METTL14 on OSCC cell proliferation. METTL14 induced m6A modification of MALAT1 to upregulate MALAT1. MALAT1 is comparatively bound to miR-224-5p to promote KDM2A transcription. In vivo, METTL14 promoted tumor growth via regulating MALAT1/miR-224-5p/ KDM2A.

Conclusions: Overall, our findings verified the therapeutic role of silencing METTL14 in OSCC treatment through the MALAT1/miR-224-5p/KDM2A axis.

Keywords: LncRNA MALAT1; METTL14; m6A; miR-224-5p; oral squamous cell carcinoma.

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell* / genetics
  • Carcinoma, Squamous Cell* / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • F-Box Proteins* / genetics
  • F-Box Proteins* / metabolism
  • Gene Expression Regulation, Neoplastic
  • Head and Neck Neoplasms* / genetics
  • Humans
  • Jumonji Domain-Containing Histone Demethylases / genetics
  • Jumonji Domain-Containing Histone Demethylases / metabolism
  • Methyltransferases / genetics
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Mouth Neoplasms* / genetics
  • Mouth Neoplasms* / pathology
  • RNA, Long Noncoding* / genetics
  • Squamous Cell Carcinoma of Head and Neck / genetics


  • MicroRNAs
  • RNA, Long Noncoding
  • KDM2A protein, human
  • F-Box Proteins
  • Jumonji Domain-Containing Histone Demethylases
  • METTL14 protein, human
  • Methyltransferases
  • MIRN224 microRNA, human