Systematic analysis of lncrna and microrna dynamic features reveals diagnostic and prognostic biomarkers of myocardial infarction

Abstract

Analyses of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) implicated in myocardial infarction (MI) have increased our understanding of gene regulatory mechanisms in MI. However, it is not known how their expression fluctuates over the different stages of MI progression. In this study, we used time-series gene expression data to examine global lncRNA and miRNA expression patterns during the acute phase of MI and at three different time points thereafter. We observed that the largest expression peak for mRNAs, lncRNAs, and miRNAs occurred during the acute phase of MI and involved mainly protein-coding, rather than non-coding RNAs. Functional analysis indicated that the lncRNAs and miRNAs most sensitive to MI and most unstable during MI progression were usually related to fewer biological functions. Additionally, we developed a novel computational method for identifying dysregulated competing endogenous lncRNA-miRNA-mRNA triplets (LmiRM-CTs) during MI onset and progression. As a result, a new panel of candidate diagnostic biomarkers defined by seven lncRNAs was suggested to have high classification performance for patients with or without MI, and a new panel of prognostic biomarkers defined by two lncRNAs evidenced high discriminatory capability for MI patients who developed heart failure from those who did not.