Elevated N6-Methyladenosine (m6A)-RNA-Methylation During Oral Carcinogenesis

Area of Science:

• Epigenetics
• Molecular Biology
• Oncology

Background:

• Oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC) involve molecular changes during malignant transformation.
• The role of N6-methyladenosine (m6A)-RNA methylation in OED and OSCC tumorigenesis is not well understood.

Purpose of the Study:

• Investigate OED and OSCC from an epigenetic viewpoint.
• Elucidate the molecular mechanisms of malignant transformation in oral tissues.
• Determine the involvement of m6A-RNA methylation in OED and OSCC.

Main Methods:

• Laser microdissection of OED and OSCC samples.
• Methylated RNA immunoprecipitation sequencing (MeRIP-Seq) for m6A modification profiling.
• RNA sequencing (RNA-seq) for gene expression analysis.

Main Results:

• Comprehensive m6A-RNA methylation and gene expression profiles were established for OED and OSCC.
• Identified four hypermethylated and 11 hypomethylated genes common to both conditions.
• Found 107 upregulated and 37 downregulated genes; C4B, DNAH9, and NCALD showed hypermethylation and upregulation, associated with better survival.

Conclusions:

• m6A-RNA methylation levels are elevated in OED and OSCC epithelial tissues compared to normal oral epithelium.
• m6A-RNA methylation is implicated in the development and progression of OED to OSCC.
• Hypermethylation and upregulation of C4B, DNAH9, and NCALD are linked to a favorable prognosis in OED and OSCC.