Characterization of dysregulated lncRNA-mRNA network based on ceRNA hypothesis to reveal the occurrence and recurrence of myocardial infarction

Abstract

Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) play important roles in initiation and development of human diseases. However, the mechanism of ceRNA regulated by lncRNA in myocardial infarction (MI) remained unclear. In this study, we performed a multi-step computational method to construct dysregulated lncRNA-mRNA networks for MI occurrence (DLMN_MI_OC) and recurrence (DLMN_MI_Re) based on “ceRNA hypothesis”. We systematically integrated lncRNA and mRNA expression profiles and miRNA-target regulatory interactions. The constructed DLMN_MI_OC and DLMN_MI_Re both exhibited biological network characteristics, and functional analysis demonstrated that the networks were specific for MI. Additionally, we identified some lncRNA-mRNA ceRNA modules involved in MI occurrence and recurrence. Finally, two new panel biomarkers defined by four lncRNAs (RP1-239B22.5, AC135048.13, RP11-4O1.2, RP11-285F7.2) from DLMN_MI_OC and three lncRNAs (RP11-363E7.4, CTA-29F11.1, RP5-894A10.6) from DLMN_MI_Re with high classification performance were, respectively, identified in distinguishing controls from patients, and patients with recurrent events from those without recurrent events. This study will provide us new insight into ceRNA-mediated regulatory mechanisms involved in MI occurrence and recurrence, and facilitate the discovery of candidate diagnostic and prognosis biomarkers for MI.

Identification of functional lncRNAs in atrial fibrillation by integrative analysis of the lncRNA‐mRNA network based on competing endogenous RNAs hypothesis

“…We found that two lncRNAs (RP11‐363E7.4 and GAS5) were all critical in each topological feature (Figure c), implying that they may exert crucial regulatory roles in AF. RP11‐363E7.4 has been identified to play important roles by acting as a ceRNA in other cardiac diseases, such as myocardial infarction (G. Zhang et al, ). GAS5 was reported to function as a regulator of cellular growth and proliferation.…”

“…Studies indicated that reanalysis of microarray probes could facilitate the discovery of new transcripts’ expression data (Liao et al, ). To obtain both lncRNAs and mRNAs expression profiles, we performed a probe reannotation pipeline as described in previous studies (Du et al, ; G. Zhang et al, ). First, the probe sequences for Affymetrix HG‐U133B array from the Affymetrix website (http://www.affymetrix.com) were remapped to the human genome (GRCH38) using SeqMap tool (Jiang & Wong, ).…”

Weighted gene co‑expression network analysis to identify key modules and hub genes associated with atrial fibrillation

“…Reannotation of microarray probes improves accuracy and makes it possible to identify new transcripts (18). Therefore, the probes of HG-U133_ Plus_2.0 array in the dataset was reannotated based on a similar method used in previous studies (19,20). The probe sequences were downloaded from Affymetrix (affymetrix.com), and remapped to the human genome (GRCh38 release 94 primary assembly; ensembl.org/index.html) using the R package 'Rsubread' (http://www.bioconductor.…”

Circulating non-coding RNAs in recurrent and metastatic ovarian cancer

“…A ceRNA involves immediate interactions between RNA molecules due to interactions with common miRNAs [77][78][79] . CeRNAs include protein coding RNAs (mRNAs), as well as lncRNAs [80,81] , pseudogenes [82,83] and circRNAs (see below). Usually, when linked to Argonaute proteins in the RNA-induced silencing complexes, miRNAs can modify protein synthesis by binding to miRNA response elements (MREs) that are present on the 3'UTR of mRNAs leading to either mRNA degradation or inhibition of the mRNA translation into proteins [42] .…”