Construction and analysis for differentially expressed long non-coding RNAs and mRNAs in acute myocardial infarction

Abstract

Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides. Some lncRNAs are related to acute myocardial infarction (AMI) and can serve as blood-based biomarkers for AMI detection. To identify whether new lncRNAs participate in AMI, the expression of lncRNAs and mRNAs was analysed by microarray analysis (Agilent human array) with the limma package in R in two series: five paired peripheral blood mononuclear cell (PBMC) samples and four paired plasma samples from different AMI patients. In PBMCs, a total of 2677 upregulated and 458 downregulated lncRNAs were significantly differentially expressed; additionally, 1168 mRNAs were upregulated and 1334 mRNAs were downregulated between the AMI patients and controls. In plasma, we found 41 upregulated and 51 downregulated lncRNAs that were differentially expressed, as well as 9 mRNAs that were upregulated and 9 mRNAs that were downregulated among the two groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the clusterProfiler package in R, and differentially expressed mRNAs were functionally annotated. The top differentially expressed mRNAs were associated with circadian rhythm, the NF-kB pathway, the p53 pathway and the metabolism pathway. We further performed target gene prediction and coexpression analysis and revealed the interrelationships among the significantly differentially expressed lncRNAs and mRNAs. The expression of four lncRNAs (uc002ddj.1, NR_047662, ENST00000581794.1 and ENST00000509938.1) was validated in the newly diagnosed AMI and control groups by quantitative real-time PCR (qRT-PCR). Our study demonstrated that the clustered expression of lncRNAs between PBMCs and plasma showed tremendous differences. The newly screened lncRNAs may play indispensable roles in the development of AMI, although their biological functions need to be further validated. Acute myocardial infarction (AMI) continues to be the primary cause of disability and death, inducing a major health burden worldwide 1. In the last decade, therapeutic methods, such as coronary intervention, coronary artery bypass surgery and medications, have ameliorated the prognosis of AMI, although its mortality remains nearly as high as before. Thus, it is critical to initiate the early identification and risk stratification of AMI, which would greatly accelerate early intervention 2,3. Advances in genome-wide analyses, especially microarray profiling, play a potential role in discovering novel clinical biomarkers for AMI 4,5. Recently, in the field of AMI, long noncoding RNAs (lncRNAs) have attracted extensive attention. LncRNAs, ranging from 200 nucleotides to >10000 nucleotides in length 6 , lack protein coding capability since they have no open reading frames (ORFs). LncRNAs have been demonstrated to participate in specific physiological and pathological processes in a wide range of cardiovascular diseases (CVDs), such as heart failure 7-9 ,

Expression of lncRNA APF in Peripheral Blood of Patients with Acute Myocardial Infarction Caused by Coronary Heart Disease and its Clinical Significance

“…Some lncRNAs are associated with AMI and can be used as blood biomarkers for AMI detection. 33) To the best of our knowledge, all these results first suggested that lncRNA APF level could assist in the diagnosis of AMI.…”

Expression Profiles and Functional Analysis of Plasma Exosomal Circular RNAs in Acute Myocardial Infarction

“…Exosomal circRNAs have become a key hotspot in the field of RNA research, especially with the rapid development and extensive application of exosome extraction and RNA sequencing technology. Accumulating evidence now indicates that exosomal microRNAs and long non-coding RNAs play a pivotal role in the pathology of atherosclerotic cardiovascular disease including CAD and AMI [ 38 – 40 ]. Li et al and Wang et al both reported that the expression patterns of exosomal circRNAs were significantly different in AMI when compared to healthy controls and play an important role in the pathological process of AMI [ 41 , 42 ].…”

Transcriptomic Profiling Unravels Novel Deregulated Gene Signatures Associated with Acute Myocardial Infarction: A Bioinformatics Approach

“…STAT1 participates in cardiomyocyte apoptosis by activating caspase-1 in response to IFN-γ during ischemia and reperfusion episodes [ 54 ]. Consequently, the deficiency of STAT1 could impart rescuing effects on AMI in terms of smaller infarcts, and increased levels of autophagy [ 55 , 56 ]. Recently, STAT1 has also been reported to have higher connectivity degrees (>20) at PPI network analysis in AMI [ 56 ].…”

“…Consequently, the deficiency of STAT1 could impart rescuing effects on AMI in terms of smaller infarcts, and increased levels of autophagy [ 55 , 56 ]. Recently, STAT1 has also been reported to have higher connectivity degrees (>20) at PPI network analysis in AMI [ 56 ]. In line with our studies, this study also identified STAT1 as a central TF that targets several crucial genes, demonstrating its potential in AMI pathology ( Figure 5 A).…”