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Lipopolysaccharide Alters the m6A Epitranscriptomic Tagging of RNAs in Cardiac Tissue

N6-methyladenosine (m(6)A) modification plays important roles in the pathology of a variety of diseases. However, the roles of m(6)A modification in sepsis-induced myocardial dysfunction are not well defined. Rats were divided into control and lipopolysaccharide (LPS)-induced sepsis group. Global m(...

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Detalles Bibliográficos
Autores principales: Han, Ye-Chen, Xie, Hong-Zhi, Lu, Bo, Xiang, Ruo-Lan, Zhang, Hai-Peng, Li, Jing-Yi, Zhang, Shu-Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355517/
https://www.ncbi.nlm.nih.gov/pubmed/34395520
http://dx.doi.org/10.3389/fmolb.2021.670160
Descripción
Sumario:N6-methyladenosine (m(6)A) modification plays important roles in the pathology of a variety of diseases. However, the roles of m(6)A modification in sepsis-induced myocardial dysfunction are not well defined. Rats were divided into control and lipopolysaccharide (LPS)-induced sepsis group. Global m(6)A levels of left ventricle tissue were measured by LC-MS/MS, and transcriptome-wide m(6)A modifications were profiled using epitranscriptomic microarrays (mRNAs and lncRNAs). Bioinformatics analysis was conducted to understand the functional implications of m(6)A modifications during sepsis. Methylated lncRNAs and mRNAs were measured by m(6)A single-base site qPCR. The global m(6)A levels in left ventricle tissue were significantly decreased in the LPS group. While 27 transcripts (23 mRNAs and four lncRNAs) were hypermethylated, 46 transcripts (39 mRNAs and 7 lncRNAs) were hypomethylated in the LPS group. The mRNA expression of writers and readers was significantly decreased in the LPS group. The m(6)A modification of Clec1b, Stk38l and Tnfrsf26 was associated with platelet activation and apoptotic pathways. Moreover, the decrease in m(6)A modification of lncRNA XR_346,771 may be related to cation import in cardiac tissue. Our data provide novel information regarding changes to m(6)A modifications in cardiac tissue during sepsis, and m(6)A modifications might be promising therapeutic targets.