Transcriptome-wide N6-methyladenosine methylation profile of atherosclerosis in mice
Abstract Background Atherosclerosis (AS) is a critical pathological event during the progression of cardiovascular diseases. It exhibits fibrofatty lesions on the arterial wall and lacks effective treatment. N6-methyladenosine (m6A) is the most common modification of eukaryotic RNA and plays an impo...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-12-01
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| Series: | BMC Genomics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12864-023-09878-1 |
| _version_ | 1797388457225486336 |
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| author | Xinbin Zheng Bo Zhou Yuzhen Li Hengren Zhong Zhengxin Huang Minhua Gu |
| author_facet | Xinbin Zheng Bo Zhou Yuzhen Li Hengren Zhong Zhengxin Huang Minhua Gu |
| author_sort | Xinbin Zheng |
| collection | DOAJ |
| description | Abstract Background Atherosclerosis (AS) is a critical pathological event during the progression of cardiovascular diseases. It exhibits fibrofatty lesions on the arterial wall and lacks effective treatment. N6-methyladenosine (m6A) is the most common modification of eukaryotic RNA and plays an important role in regulating the development and progression of cardiovascular diseases. However, the role of m6A modification in AS remains largely unknown. Therefore, in this study, we explored the transcriptome distribution of m6A modification in AS and its potential mechanism. Methods Methylation Quantification Kit was used to detect the global m6A levels in the aorta of AS mice. Western blot was used to analyze the protein level of methyltransferases. Methylated RNA immunoprecipitation with next-generation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) were used to obtain the first transcriptome range analysis of the m6A methylene map in the aorta of AS mice, followed by bioinformatics analysis. qRT-PCR and MeRIP-qRT-PCR were used to measure the mRNA and m6A levels in target genes. Results The global m6A and protein levels of methyltransferase METTL3 were significantly increased in the aorta of AS mice. However, the protein level of demethylase ALKBH5 was significantly decreased. Through MeRIP-seq, we obtained m6A methylation maps in AS and control mice. In total, 26,918 m6A peaks associated with 13,744 genes were detected in AS group, whereas 26,157 m6A peaks associated with 13,283 genes were detected in the control group. Peaks mainly appeared in the coding sequence (CDS) regions close to the stop codon with the RRACH motif. Moreover, functional enrichment analysis demonstrated that m6A-containing genes were significantly enriched in AS-relevant pathways. Interestingly, a negative correlation between m6A methylation abundance and gene expression level was found through the integrated analysis of MeRIP-seq and RNA-seq data. Among the m6A-modified genes, a hypo-methylated but up-regulated (hypo-up) gene Fabp5 may be a potential biomarker of AS. Conclusions Our study provides transcriptome-wide m6A methylation for the first time to determine the association between m6A modification and AS progression. Our study lays a foundation for further exploring the pathogenesis of AS and provides a new direction for the treatment of AS. |
| first_indexed | 2024-03-08T22:41:05Z |
| format | Article |
| id | doaj.art-2679773597b24cb0ace487be568c275b |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-03-08T22:41:05Z |
| publishDate | 2023-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-2679773597b24cb0ace487be568c275b2023-12-17T12:07:54ZengBMCBMC Genomics1471-21642023-12-0124111110.1186/s12864-023-09878-1Transcriptome-wide N6-methyladenosine methylation profile of atherosclerosis in miceXinbin Zheng0Bo Zhou1Yuzhen Li2Hengren Zhong3Zhengxin Huang4Minhua Gu5Clinical Research Center, Hainan Provincial Hospital of Traditional Chinese MedicineDepartment of Cardiology, Hainan Provincial Hospital of Traditional Chinese MedicineClinical Research Center, Hainan Provincial Hospital of Traditional Chinese MedicineClinical Research Center, Hainan Provincial Hospital of Traditional Chinese MedicineDepartment of Cardiology, Hainan Provincial Hospital of Traditional Chinese MedicineDepartment of Cardiology, Hainan Provincial Hospital of Traditional Chinese MedicineAbstract Background Atherosclerosis (AS) is a critical pathological event during the progression of cardiovascular diseases. It exhibits fibrofatty lesions on the arterial wall and lacks effective treatment. N6-methyladenosine (m6A) is the most common modification of eukaryotic RNA and plays an important role in regulating the development and progression of cardiovascular diseases. However, the role of m6A modification in AS remains largely unknown. Therefore, in this study, we explored the transcriptome distribution of m6A modification in AS and its potential mechanism. Methods Methylation Quantification Kit was used to detect the global m6A levels in the aorta of AS mice. Western blot was used to analyze the protein level of methyltransferases. Methylated RNA immunoprecipitation with next-generation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) were used to obtain the first transcriptome range analysis of the m6A methylene map in the aorta of AS mice, followed by bioinformatics analysis. qRT-PCR and MeRIP-qRT-PCR were used to measure the mRNA and m6A levels in target genes. Results The global m6A and protein levels of methyltransferase METTL3 were significantly increased in the aorta of AS mice. However, the protein level of demethylase ALKBH5 was significantly decreased. Through MeRIP-seq, we obtained m6A methylation maps in AS and control mice. In total, 26,918 m6A peaks associated with 13,744 genes were detected in AS group, whereas 26,157 m6A peaks associated with 13,283 genes were detected in the control group. Peaks mainly appeared in the coding sequence (CDS) regions close to the stop codon with the RRACH motif. Moreover, functional enrichment analysis demonstrated that m6A-containing genes were significantly enriched in AS-relevant pathways. Interestingly, a negative correlation between m6A methylation abundance and gene expression level was found through the integrated analysis of MeRIP-seq and RNA-seq data. Among the m6A-modified genes, a hypo-methylated but up-regulated (hypo-up) gene Fabp5 may be a potential biomarker of AS. Conclusions Our study provides transcriptome-wide m6A methylation for the first time to determine the association between m6A modification and AS progression. Our study lays a foundation for further exploring the pathogenesis of AS and provides a new direction for the treatment of AS.https://doi.org/10.1186/s12864-023-09878-1AtherosclerosisN6-methyladenosineMeRIP-seqFabp5 |
| spellingShingle | Xinbin Zheng Bo Zhou Yuzhen Li Hengren Zhong Zhengxin Huang Minhua Gu Transcriptome-wide N6-methyladenosine methylation profile of atherosclerosis in mice BMC Genomics Atherosclerosis N6-methyladenosine MeRIP-seq Fabp5 |
| title | Transcriptome-wide N6-methyladenosine methylation profile of atherosclerosis in mice |
| title_full | Transcriptome-wide N6-methyladenosine methylation profile of atherosclerosis in mice |
| title_fullStr | Transcriptome-wide N6-methyladenosine methylation profile of atherosclerosis in mice |
| title_full_unstemmed | Transcriptome-wide N6-methyladenosine methylation profile of atherosclerosis in mice |
| title_short | Transcriptome-wide N6-methyladenosine methylation profile of atherosclerosis in mice |
| title_sort | transcriptome wide n6 methyladenosine methylation profile of atherosclerosis in mice |
| topic | Atherosclerosis N6-methyladenosine MeRIP-seq Fabp5 |
| url | https://doi.org/10.1186/s12864-023-09878-1 |
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