Expression Pattern and Clinical Value of Key m6A RNA Modification Regulators in Abdominal Aortic Aneurysm

Tan Li,1 Tianlong Wang,2 Jingjing Jing,3,4 Liping Sun3,4 1Department of Cardiovascular Ultrasound, The First Hospital of China Medical University, Shenyang, People’s Republic of China; 2The First Clinical College of China Medical University, The First Hospital of China Medical University, Shenyang,...

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Autores principales:	Li T, Wang T, Jing J, Sun L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	abdominal aortic aneurysm gene expression m6a modification Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/ebf08dc9cbfd41ee9bf92e65ee2414c6
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spelling	oai:doaj.org-article:ebf08dc9cbfd41ee9bf92e65ee2414c62021-12-02T15:09:50ZExpression Pattern and Clinical Value of Key m6A RNA Modification Regulators in Abdominal Aortic Aneurysm1178-7031https://doaj.org/article/ebf08dc9cbfd41ee9bf92e65ee2414c62021-08-01T00:00:00Zhttps://www.dovepress.com/expression-pattern-and-clinical-value-of-key-m6a-rna-modification-regu-peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Tan Li,1 Tianlong Wang,2 Jingjing Jing,3,4 Liping Sun3,4 1Department of Cardiovascular Ultrasound, The First Hospital of China Medical University, Shenyang, People’s Republic of China; 2The First Clinical College of China Medical University, The First Hospital of China Medical University, Shenyang, People’s Republic of China; 3Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, Shenyang, People’s Republic of China; 4Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department, The First Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Liping SunTumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, No. 155 NanjingBei Street, Heping District, Shenyang, Liaoning Province, 110001, People’s Republic of ChinaTel +86-24-83282153Fax +86-24-83282383Email lipingsun@hotmail.comBackground: Aberrant expression of N6-methyladenosine (m6A) RNA modification regulators plays a critical role in a variety of human diseases. However, their implication in abdominal aortic aneurysm (AAA) remains largely unknown. Herein, we sought to explore the general expression pattern and potential functions of m6A regulators in AAA.Methods: We analyzed gene expression data of m6A regulators in human AAA and normal tissues from public GEO database. The R package and other tools such as m6A2Target database, Gene ontology (GO) functional and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses, gene set variation analysis (GSVA), Search Tool for the Retrieval of Interacting Genes (STRING), starBase, miRDB and Cytoscape software were applied for bioinformatics analysis to investigate the downstream molecular mechanisms and upstream regulatory mechanisms for distinctly expressed regulators. Quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were performed to validate the expression of key m6A regulators in our collected human AAA specimens.Results: We found that METTL14 and HNRNPC were the downregulated m6A regulators, and RBM15B was the upregulated methylation transferase in human AAA. The modified genes were primarily enriched in RNA catabolic process, regulation of translation, focal adhesion, transcription coregulator activity, ribosome, RNA transport, cell cycle, et al. METTL14, HNRNPC and RBM15B levels were correlated with the immune infiltration degree of Tcm, macrophages, mast cells, Tgd and NK CD56bright cells. A total of 154 and 76 target genes of three regulators were separately involved in body metabolism and autophagy in AAA disease, and their interactive relationships and hub genes were identified. The lncRNA-miRNA-mRNA interaction regulatory networks were also constructed for METTL14, HNRNPC and RBM15B. Based on our clinical tissue and serum samples, METTL14 exhibited lower expression levels in AAA and its rupture type, and low METTL14 expression was associated with high levels of WBC and CRP (all P < 0.05).Conclusion: Our study presents an overview of the expression pattern and functional significance of m6A regulators in human AAA. Our findings will provide a valuable resource that may guide both mechanistic and therapeutic analyses about the role of key m6A regulators in AAA.Keywords: abdominal aortic aneurysm, gene expression, m6A modificationLi TWang TJing JSun LDove Medical Pressarticleabdominal aortic aneurysmgene expressionm6a modificationPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 4245-4258 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	abdominal aortic aneurysm gene expression m6a modification Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	abdominal aortic aneurysm gene expression m6a modification Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Li T Wang T Jing J Sun L Expression Pattern and Clinical Value of Key m6A RNA Modification Regulators in Abdominal Aortic Aneurysm
description	Tan Li,1 Tianlong Wang,2 Jingjing Jing,3,4 Liping Sun3,4 1Department of Cardiovascular Ultrasound, The First Hospital of China Medical University, Shenyang, People’s Republic of China; 2The First Clinical College of China Medical University, The First Hospital of China Medical University, Shenyang, People’s Republic of China; 3Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, Shenyang, People’s Republic of China; 4Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department, The First Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Liping SunTumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, No. 155 NanjingBei Street, Heping District, Shenyang, Liaoning Province, 110001, People’s Republic of ChinaTel +86-24-83282153Fax +86-24-83282383Email lipingsun@hotmail.comBackground: Aberrant expression of N6-methyladenosine (m6A) RNA modification regulators plays a critical role in a variety of human diseases. However, their implication in abdominal aortic aneurysm (AAA) remains largely unknown. Herein, we sought to explore the general expression pattern and potential functions of m6A regulators in AAA.Methods: We analyzed gene expression data of m6A regulators in human AAA and normal tissues from public GEO database. The R package and other tools such as m6A2Target database, Gene ontology (GO) functional and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses, gene set variation analysis (GSVA), Search Tool for the Retrieval of Interacting Genes (STRING), starBase, miRDB and Cytoscape software were applied for bioinformatics analysis to investigate the downstream molecular mechanisms and upstream regulatory mechanisms for distinctly expressed regulators. Quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were performed to validate the expression of key m6A regulators in our collected human AAA specimens.Results: We found that METTL14 and HNRNPC were the downregulated m6A regulators, and RBM15B was the upregulated methylation transferase in human AAA. The modified genes were primarily enriched in RNA catabolic process, regulation of translation, focal adhesion, transcription coregulator activity, ribosome, RNA transport, cell cycle, et al. METTL14, HNRNPC and RBM15B levels were correlated with the immune infiltration degree of Tcm, macrophages, mast cells, Tgd and NK CD56bright cells. A total of 154 and 76 target genes of three regulators were separately involved in body metabolism and autophagy in AAA disease, and their interactive relationships and hub genes were identified. The lncRNA-miRNA-mRNA interaction regulatory networks were also constructed for METTL14, HNRNPC and RBM15B. Based on our clinical tissue and serum samples, METTL14 exhibited lower expression levels in AAA and its rupture type, and low METTL14 expression was associated with high levels of WBC and CRP (all P < 0.05).Conclusion: Our study presents an overview of the expression pattern and functional significance of m6A regulators in human AAA. Our findings will provide a valuable resource that may guide both mechanistic and therapeutic analyses about the role of key m6A regulators in AAA.Keywords: abdominal aortic aneurysm, gene expression, m6A modification
format	article
author	Li T Wang T Jing J Sun L
author_facet	Li T Wang T Jing J Sun L
author_sort	Li T
title	Expression Pattern and Clinical Value of Key m6A RNA Modification Regulators in Abdominal Aortic Aneurysm
title_short	Expression Pattern and Clinical Value of Key m6A RNA Modification Regulators in Abdominal Aortic Aneurysm
title_full	Expression Pattern and Clinical Value of Key m6A RNA Modification Regulators in Abdominal Aortic Aneurysm
title_fullStr	Expression Pattern and Clinical Value of Key m6A RNA Modification Regulators in Abdominal Aortic Aneurysm
title_full_unstemmed	Expression Pattern and Clinical Value of Key m6A RNA Modification Regulators in Abdominal Aortic Aneurysm
title_sort	expression pattern and clinical value of key m6a rna modification regulators in abdominal aortic aneurysm
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/ebf08dc9cbfd41ee9bf92e65ee2414c6
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Expression Pattern and Clinical Value of Key m6A RNA Modification Regulators in Abdominal Aortic Aneurysm

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