Identification of long non-coding RNAs biomarkers for early diagnosis of myocardial infarction from the dysregulated coding-non-coding co-expression network

Abstract

Long non-coding RNAs (lncRNAs) have recently been shown as novel promising diagnostic or prognostic biomarkers for various cancers. However, lncRNA expression patterns and their predictive value in early diagnosis of myocardial infarction (MI) have not been systematically investigated. In our study, we performed a comprehensive analysis of lncRNA expression profiles in MI and found altered lncRNA expression pattern in MI compared to healthy samples. We then constructed a lncRNA-mRNA dysregulation network (DLMCEN) by integrating aberrant lncRNAs, mRNAs and their co-dysregulation relationships, and found that some of mRNAs were previously reported to be involved in cardiovascular disease, suggesting the functional roles of dysregulated lncRNAs in the pathogenesis of MI. Therefore, using support vector machine (SVM) and leave one out cross-validation (LOOCV), we developed a 9-lncRNA signature (termed 9LncSigAMI) from the discovery cohort which could distinguish MI patients from healthy samples with accuracy of 95.96%, sensitivity of 93.88% and specificity of 98%, and validated its predictive power in early diagnosis of MI in another completely independent cohort. Functional analysis demonstrated that these nine lncRNA biomarkers in the 9LncSigAMI may be involved in myocardial innate immune and inflammatory response, and their deregulation may lead to the dysfunction of the inflammatory and immune system contributing to MI recurrence. With prospective validation, the 9LncSigAMI identified by our work will provide additional diagnostic information beyond other known clinical parameters, and increase the understanding of the molecular mechanism underlying the pathogenesis of MI.

LncRNA‐RP11‐714G18.1 suppresses vascular cell migration via directly targeting LRP2BP

“…Moreover, they have been shown to serve as molecular scaffolds for nuclear compartmentalization, recruiters for chromatin‐modifying complexes, miRNA sponges and gene controllers for sequestration . Considering that lncRNAs play a diverse role in cellular networks, they have been implicated as contributing factors to many human disorders, such as cancers, neurological disorders, and CVD . It has been shown that aberrant lncRNAs expression can result in dysregulation of downstream effector molecules and consequently lead to the pathogenesis of CVD.…”

“…8 Considering that lncRNAs play a diverse role in cellular networks, they have been implicated as contributing factors to many human disorders, such as cancers, neurological disorders, and CVD. [9][10][11] It has been shown that aberrant lncRNAs expression can result in dysregulation of downstream effector molecules and consequently lead to the pathogenesis of CVD. Recent studies also showed that lncRNAs were pivotal regulators of VSMCs and ECs proliferation, migration, and cell motility.…”

Identification of lncRNAs involved in biological regulation in early age-related macular degeneration

“…24 In a study on myocardial infarction and lncRNA expression profiles, the functional analysis demonstrated that a total of 9 lncRNAs were involved in myocardial innate immune responses, and the dysregulation of these lncRNAs led to abnormalities of the immune system. 25 Knowledge on the regulatory effects of lncRNAs on AMD progression, and the detailed functions of lncRNAs on the incidence of early AMD, is quite limited. In a previous study, the detection of dysregulated lncRNAs in pathological neovascularization provided evidences of late AMD development.…”

LncRNA260-specific siRNA targeting IL28RA gene inhibit cardiomyocytes hypoxic/reoxygenation injury

“…Recently, some studies have suggested long non-coding RNAs (lncRNAs) in cardiovascular physiology and the initiation and progression of cardiovascular disease (6)(7)(8). Early on in our study, we tested what genes were regulated by lncRNA260 by high throughput RNA and lncRNA chips screening and found that only the IL28RA gene was the only gene to be regulated by lncRNA260.…”