Transcriptome Profiling of N7-Methylguanosine Modification of Messenger RNA in Drug-Resistant Acute Myeloid Leukemia

Abstract

Acute myeloid leukemia (AML) is an aggressive hematological tumor caused by the malignant transformation of myeloid progenitor cells. Although intensive chemotherapy leads to an initial therapeutic response, relapse due to drug resistance remains a significant challenge. In recent years, accumulating evidence has suggested that post-transcriptional methylation modifications are strongly associated with tumorigenesis. However, the mRNA profile of m7G modification in AML and its role in drug-resistant AML are unknown. In this study, we used MeRIP-seq technology to establish the first transcriptome-wide m7G methylome profile for AML and drug-resistant AML cells, and differences in m7G between the two groups were analyzed. In addition, bioinformatics analysis was conducted to explore the function of m7G-specific methylated transcripts. We found significant differences in m7G mRNA modification between AML and drug-resistant AML cells. Furthermore, bioinformatics analysis revealed that differential m7G-modified mRNAs were associated with a wide range of cellular functions. Importantly, down-methylated m7G modification was significantly enriched in ABC transporter-related mRNAs, which are widely recognized to play a key role in multidrug resistance. Our results provide new insights into a novel function of m7G methylation in drug resistance progression of AML.