METTL11A serves as a novel therapeutic target for acute myeloid leukemia through regulation of the p38-MAPK pathway.

BACKGROUND

Acute myeloid leukemia (AML) represents a heterogeneous blood malignancy and is the most common and severe acute leukemia in adult. The METTL gene family is increasingly being recognized as involved in cancer progression. The aim of the study is to elaborate on the specific role of METTL11A in AML.

METHODS

In this research, cell viability, transwell assay, and scratch wound assay were utilized to assess cell proliferation and migration in AML cells. Western blot was used to determine the expression of proteins and the activation of signal pathway. Virtual screening was performed to obtain potential inhibitors of METTL11A.

RESULTS

Our findings indicated that METTL11A expression levels were strongly associated with AML patients' prognosis. Overexpressed METTL11A by constructing stable cell lines promoted proliferation and migration in AML cells. Conversely, knockdown of METTL11A inhibited cell viability and migration. Through gene sets enrichment analysis, we validated the inactivated p38-mitogen-activated protein kinase (MAPK) pathway under silenced METTL11A expression. In high throughput molecular docking, S-Adenosyl-L-methionine disulfate tosylate was predicted to bind METTL11A, which was validated to inhibit cell proliferation and migration.

CONCLUSIONS

The results suggested that METTL11A is a novel biomarker and therapeutic target in AML, which is mediated by suppressed MAPK pathway.