Dataset Information

Distinct N7-methylguanosine profiles of circular RNAs in drug-resistant acute myeloid leukemia.

ABSTRACT: Post-transcriptional methylation modifications, such as the N7-methylguanosine (m7G) modification, are increasingly acknowledged for their role in the development and resistance to chemotherapy in acute myeloid leukemia (AML). This study employed MeRIP-seq technology to investigate the m7G sites within circular RNAs (circRNAs) derived from human AML cells and drug-resistant AML cells, in order to identify these sites more comprehensively. In addition, a detailed analysis of the relationship between m7G and drug-resistant AML was conducted. The bioinformatics analysis was utilized to predict the functions of specific methylated transcripts. The findings revealed a significant difference in m7G level between AML cells and drug-resistant AML cells, suggesting a potentially critical role of m7G in circRNAs in drug-resistant AML development. The methylation of M7G could affect the circRNA-miRNA-mRNA co-expression during the development of AML resistance, which could further influence the regulation of resistance-associated target genes in AML. Furthermore, gene ontology analysis indicated that the distinct distribution pattern of circRNAs with m7G methylation in drug-resistant AML cells was correlated with metabolism-related pathways. These results suggested a potential association between drug-resistant AML and m7G methylation of circRNAs. Moreover, the results revealed a novel role of m7G RNA methylation in circRNAs in the progression of AML chemoresistance.

SUBMITTER: Fu J

PROVIDER: S-EPMC10485064 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Distinct N7-methylguanosine profiles of circular RNAs in drug-resistant acute myeloid leukemia.

Fu Jinqiu J Si Libo L Zhou Yao Y Li Dong D Wang Ran R

Scientific reports 20230907 1

Post-transcriptional methylation modifications, such as the N7-methylguanosine (m7G) modification, are increasingly acknowledged for their role in the development and resistance to chemotherapy in acute myeloid leukemia (AML). This study employed MeRIP-seq technology to investigate the m7G sites within circular RNAs (circRNAs) derived from human AML cells and drug-resistant AML cells, in order to identify these sites more comprehensively. In addition, a detailed analysis of the relationship betw ...[more]

PMID: 37679400

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Project description:BackgroundGrowing evidence indicates that RNA methylation plays a fundamental role in epigenetic regulation, which is associated with the tumorigenesis and drug resistance. Among them, acute myeloid leukemia (AML), as the top acute leukemia for adults, is a deadly disease threatening human health. Although N7-methylguanosine (m7G) has been identified as an important regulatory modification, its distribution has still remained elusive.MethodsThe present study aimed to explore the long non-coding RNA (lncRNA) functional profile of m7G in AML and drug-resistant AML cells. The transcriptome-wide m7G methylation of lncRNA was analyzed in AML and drug-resistant AML cells. RNA MeRIP-seq was performed to identify m7G peaks on lncRNA and differences in m7G distribution between AML and drug-resistant AML cells. The Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to predict the possible roles and m7G-associated pathway.ResultsUsing m7G peak sequencing, it was found that a sequence motif was necessary for m7G methylation in drug-resistant AML lncRNA. Unsupervised hierarchical cluster analysis confirmed that lncRNA m7G methylation occurred more frequently in drug-resistant AML cells than in AML cells. RNA sequencing demonstrated that more genes were upregulated by methylation in drug-resistant AML cells, while methylation downregulated more genes in AML cells. The GO and KEGG pathway enrichment analyses revealed that genes having a significant correlation with m7G sites in lncRNA were involved in drug-resistant AML signaling pathways.ConclusionSignificant differences in the levels and patterns of m7G methylation between drug-resistant AML cells and AML cells were revealed. Furthermore, the cellular functions potentially influenced by m7G in drug-resistant AML cells were predicted, providing evidence implicating m7G-mediated lncRNA epigenetic regulation in the progression of drug resistance in AML. These findings highlight the involvement of m7G in the development of drug resistance in AML.

Project description:Background: Hepatocellular carcinoma (HCC), which has high rates of recurrence and metastasis and is the main reason and the most common tumor for cancer mortality worldwide, has an unfavorable prognosis. N7-methylguanosine (m7G) modification can affect the formation and development of tumors by affecting gene expression and other biological processes. In addition, many previous studies have confirmed the unique function of long noncoding RNAs (lncRNAs) in tumor progression; however, studies exploring the functions of m7G-related lncRNAs in HCC patients has been limited. Methods: Relevant RNA expression information was acquired from The Cancer Genome Atlas (TCGA, https://portal.gdc.cancer.gov), and m7G-related lncRNAs were identified via gene coexpression analysis. Afterward, univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and multivariate regression analyses were implemented to construct an ideal risk model whose validity was verified using Kaplan-Meier survival, principal component, receiver operating characteristic (ROC) curve, and nomogram analyses. In addition, the potential functions of lncRNAs in the novel signature were explored through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and gene set enrichment analysis (GSEA). At last, in both risk groups and subtypes classified based on the expression of the risk-related lncRNAs, we analyzed the immune characteristics and drug sensitivity of patients. Results: After rigorous screening processes, we built a model based on 11 m7G-related lncRNAs for predicting patient overall survival (OS). The results suggested that the survival status of patients with high-risk scores was lower than that of patients with low-risk scores, and a high-risk score was related to malignant clinical features. Cox regression analysis showed that the m7G risk score was an independent prognostic parameter. Moreover, immune cell infiltration and immunotherapy sensitivity differed between the risk groups. Conclusion: The m7G risk score model constructed based on 11 m7G-related lncRNAs can effectively assess the OS of HCC patients and may offer support for making individualized treatment and immunotherapy decisions for HCC patients.

Dataset Information

Distinct N7-methylguanosine profiles of circular RNAs in drug-resistant acute myeloid leukemia.

Publications

Distinct N7-methylguanosine profiles of circular RNAs in drug-resistant acute myeloid leukemia.

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