m6A甲基转移酶METTL3促进急性T淋巴细胞白血病细胞生长的研究

he Objective: Acute T-lymphoblastic leukemia (T-ALL) is a hematological malignancy caused by the malignant transformation and clonal expansion of T-lineage progenitor cells in the bone marrow and thymus. Currently, there are no targeted therapies for T-ALL. N6-methyladenosine (m6A) is a widely studied RNA modification in eukaryotic cells. Recent reports have shown that m6A modification-related regulatory proteins are implicated in the progression of T-ALL, but the role of METTL3 in T-ALL has not been elucidated. This study aimed to investigate the function of METTL3 in the growth/survival of T-ALL cells. Methods: (1) The expression levels of METTL3 in various tumor cells and T-ALL cells were downloaded and analyzed from the Depmap database and GEO database; (2) The expression of METTL3 in normal bone marrow (NBM) and T-ALL cell lines was detected by RT-qPCR and Western blot; (3) Jurkat cells were infected with lentivirus to silence METTL3, and the effects of METTL3 silencing on proliferation, colony formation, and apoptosis were analyzed; (4) The effects of METTL3 small molecule inhibitor UZH1a on the m6A modification level, proliferation, colony formation ability, and apoptosis on T-ALL cells were investigated. Results: (1) METTL3 is highly expressed in various tumors including T-ALL cells; (2) The expression of METTL3 in T-ALL cell lines is significantly higher than that in normal bone marrow cells; (3) Silence of METTL3 in vitro significantly inhibits the proliferation, colony formation, and m6A modification level of T-ALL cells and promotes; (4) UZH1a exhibits anti-leukemia effect in vitro. Conclusion: METTL3, an m6A methyltransferase, is highly expressed in T-ALL and promotes the growthof T-ALL cells.