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耐药急性髓系白血病中信使核糖核酸N7-甲基鸟苷修饰的转录组分析

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

作者信息

Zhang Bing, Li Dong, Wang Ran

机构信息

Department of Pediatrics, Qilu Hospital of Shandong University, Shandong, China.

Department of Hematology, Qilu Hospital of Shandong University, Shandong, China.

出版信息

Front Oncol. 2022 Jul 5;12:926296. doi: 10.3389/fonc.2022.926296. eCollection 2022.

DOI:10.3389/fonc.2022.926296
PMID:35865472
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9294171/
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.

摘要

急性髓系白血病(AML)是一种由髓系祖细胞恶性转化引起的侵袭性血液肿瘤。尽管强化化疗会带来初始治疗反应,但耐药导致的复发仍然是一个重大挑战。近年来,越来越多的证据表明转录后甲基化修饰与肿瘤发生密切相关。然而,AML中m7G修饰的mRNA谱及其在耐药AML中的作用尚不清楚。在本研究中,我们使用MeRIP-seq技术建立了首个AML和耐药AML细胞的全转录组范围的m7G甲基化组图谱,并分析了两组之间m7G的差异。此外,进行了生物信息学分析以探索m7G特异性甲基化转录本的功能。我们发现AML和耐药AML细胞之间m7G mRNA修饰存在显著差异。此外,生物信息学分析表明,差异m7G修饰的mRNA与广泛的细胞功能相关。重要的是,低甲基化的m7G修饰在ABC转运蛋白相关的mRNA中显著富集,而ABC转运蛋白在多药耐药中起着关键作用,这一点已得到广泛认可。我们的研究结果为m7G甲基化在AML耐药进展中的新功能提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10f1/9294171/e42ca7a868b7/fonc-12-926296-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10f1/9294171/ccf35268b828/fonc-12-926296-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10f1/9294171/ae82725de020/fonc-12-926296-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10f1/9294171/17e38ff5d333/fonc-12-926296-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10f1/9294171/0685d98791f8/fonc-12-926296-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10f1/9294171/e42ca7a868b7/fonc-12-926296-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10f1/9294171/ccf35268b828/fonc-12-926296-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10f1/9294171/ae82725de020/fonc-12-926296-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10f1/9294171/17e38ff5d333/fonc-12-926296-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10f1/9294171/0685d98791f8/fonc-12-926296-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10f1/9294171/e42ca7a868b7/fonc-12-926296-g005.jpg

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