MicroRNA-1306-5p Regulates the METTL14-Guided m6A Methylation to Repress Acute Myeloid Leukemia
COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE(2022)
Abstract
miRNA and m6A methylation are two key regulators in cancers. However, in acute myeloid leukemia (AML), the relationship of miRNA and m6A methylation remains unclear. The present work is aimed at determining the effect of m6A methylation induced by miRNAs on AML and its underlying mechanism. The expression of METTL14 was detected by qRT-PCR and western blot. The growth of HL-60 cells was analyzed by CCK-8, Transwell assay, and flow cytometry. Tumor-bearing mice were established, and Ki-67 staining assay was used to detect the proliferation in vivo. Dual luciferase reporter system detected the effect of miR-1306-5p on METTL14 luciferase activity. Dot blot analysis detected m6A methylation. We found that METTL14 was upregulated in AML patients and overexpressed METTL14 promoted AML development. Further analysis indicated that METTL14 was directly targeted by miR-1306-5p and overexpressed miR-1306-5p alleviated AML progression. In addition, m6A methylation level regulated by METTL14 could be affected by miR-1306-5p. In conclusion, we found that suppressed miR-1306-5p enhanced AML progression by elevating m6A methylation level via upregulating METTL14. These findings provided basis for the development of new strategies for treating AML.
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Key words
acute myeloid leukemia,methylation
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