METTL3-mediated ALDH m6A methylation regulates the malignant behavior of BMI1+ HNSCC stem cells

Objectives: To reveal the effect and mechanism of methyltransferase--like 3 (METTL3) on cancer stem cells (CSCs) of head and neck squamous cell carcinoma (HNSCC). Materials and Methods: First, we analyzed 14-HNSCC-patients' scRNA-seq dataset and TCGA dataset of HNSCC. Then, Mettl3 knockout or overexpression mice models were studied via tracing and staining technologies. In addition, we took flow cytometry sorting and sphere formation assays to observe tumorigenicity and used cell transfection and western blotting to verify target protein expression levels. Furthermore, methylated RNA immunoprecipitation sequencing (MeRIP-seq) and MeRIP-quantitative real-time PCR (MeRIP-qPCR) were taken to identify the mechanism of Mettl3 regulating Bmi1(+) CSCs in HNSCC. Conclusion: Regulated by SOX4, METTL3-mediated ALDH m(6)A methylation regulates the malignant behavior of BMI1(+) HNSCC CSCs through cell division pathway.

Automated summary

This study investigated the effect and mechanism of methyltransferase-like 3 (METTL3) on cancer stem cells (CSCs) in head and neck squamous cell carcinoma (HNSCC). The analysis of scRNA-seq and TCGA datasets revealed that METTL3 regulates the malignant behavior of BMI1(+) HNSCC CSCs through the cell division pathway. Knockout or overexpression models of Mettl3 were used, along with tracing and staining technologies, flow cytometry sorting, sphere formation assays, cell transfection, western blotting, and MeRIP-seq and MeRIP-qPCR techniques to validate the findings.