Transcriptome-Wide N6-Methyladenosine Methylation Landscape of Coronary Artery Disease

Abstract

Aim: To reveal transcriptome-wide N6-methyladenosine (m⁶A) methylome of coronary artery disease (CAD). Materials&methods: The m⁶A levels of RNA from peripheral blood mononuclear cells measured by colorimetry were significantly decreased in CAD cases. Transcriptome-wide m⁶A methylome profiled by methylated RNA immunoprecipitation sequencing (MeRIP-seq) identified differentially methylated m⁶A sites within both mRNAs and lncRNAs between CAD and control group. Results: Bioinformatic analysis indicated that differentially methylated genes were involved in the pathogenesis of atherosclerosis. MeRIP-quantitative real-time PCR assay confirmed the reliability of MeRIP-seq data. Finally, the rat carotid artery balloon injury model was performed to confirm the role of m⁶A demethylase FTO in neointima formation. Conclusion: Our study provided a resource of differentially methylated m⁶A profile for uncovering m⁶A biological functions in the pathogenesis of CAD.

Keywords::

• coronary artery disease
• differentially methylated m⁶A sites
• fat mass and obesity-associated protein
• neointima formation
• RNA m⁶A methylation

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2020-0372

Acknowledgments

We sincerely thank all patients and healthy volunteers who participated in this study.

Financial & competing interests disclosure

This work was supported by the Natural Science Foundation of Beijing (No.7212081 [to L Wang]); CAMS Innovation Fund for Medical Sciences (CIFMS) (No.2016-I2M-1-009 [to L Wang], 2017-I2M-1-004 [to J Li], 2016-I2M-1-011 [to X Lu], 2016-I2M-2-001 [to S Chen], 2016-I2M-3-018 [to J Chen] and 2017-I2M-1-008 [to J Cao]); the National Natural Science Foundation of China (No. 82070473 [to S Chen], No. 91857118 [to X Lu] and 81600361 [to B Yang]); the High-Tech Research and Development Program of China (863 Plan; No.2012AA02A516 [to L Wang]); and the National Basic Research Program of China (973 Plan; No.2011CB503901 [to L Wang]) from the Ministry of Science and Technology of China. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Data sharing statement

The data supporting the findings of the present study are available from corresponding author upon reasonable request.

Additional information

Funding

This work was supported by the Natural Science Foundation of Beijing (No.7212081 [to L Wang]); CAMS Innovation Fund for Medical Sciences (CIFMS) (No.2016-I2M-1-009 [to L Wang], 2017-I2M-1-004 [to J Li], 2016-I2M-1-011 [to X Lu], 2016-I2M-2-001 [to S Chen], 2016-I2M-3-018 [to J Chen] and 2017-I2M-1-008 [to J Cao]); the National Natural Science Foundation of China (No. 82070473 [to S Chen], No. 91857118 [to X Lu] and 81600361 [to B Yang]); the High-Tech Research and Development Program of China (863 Plan; No.2012AA02A516 [to L Wang]); and the National Basic Research Program of China (973 Plan; No.2011CB503901 [to L Wang]) from the Ministry of Science and Technology of China. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.