Expression Signatures of Long Noncoding RNAs in Left Ventricular Noncompaction

Abstract

Long noncoding RNAs have gained widespread attention in recent years for their crucial role in biological regulation. They have been implicated in a range of developmental processes and diseases including cancer, cardiovascular, and neuronal diseases. However, the role of long noncoding RNAs (lncRNAs) in left ventricular noncompaction (LVNC) has not been explored. In this study, we investigated the expression levels of lncRNAs in the blood of LVNC patients and healthy subjects to identify differentially expressed lncRNA that develop LVNC specific biomarkers and targets for developing therapies using biological pathways. We used Agilent Human lncRNA array that contains both updated lncRNAs and mRNAs probes. We identified 1,568 upregulated and 1,141 downregulated (log fold-change > 2.0) lncRNAs that are differentially expressed between LVNC and the control group. Among them, RP11-1100L3.7 and XLOC_002730 are the most upregulated and downregulated lncRNAs. Using quantitative real-time reverse transcription polymerase chain reaction (RT-QPCR), we confirmed the differential expression of three top upregulated and downregulated lncRNAs along with two other randomly picked lncRNAs. Gene Ontology (GO) and KEGG pathways analysis with these differentially expressed lncRNAs provide insight into the cellular pathway leading to LVNC pathogenesis. We also identified 1,066 upregulated and 1,017 downregulated mRNAs. Gene set enrichment analysis (GSEA) showed that G2M, Estrogen, and inflammatory pathways are enriched in differentially expressed genes (DEG). We also identified miRNA targets for these differentially expressed genes. In this study, we first report the use of LncRNA microarray to understand the pathogenesis of LVNC and to identify several lncRNA and genes and their targets as potential biomarkers.

Construction of a ceRNA network reveals functional lncRNAs in left ventricular noncompaction through weighted gene co-expression network analysis

“…GSEA revealed that NLRP3 in ammasome (GO), bile secretion and thyroid hormone synthesis (KEGG) were enriched in LVNC, consistent with the former study [15]. In addition, the "interstitial matrix", "endocytosis" terms were positively enriched.…”

“…We obtained human LVNC related genes from the Gene Expression Omnibus database (GEO, https://www.ncbi.nlm.nih.gov/geo). GSE178582 dataset contains blood samples from 6 LVNC patients and 6 healthy controls, pro ling mRNA and lncRNA expression [15]. GSE178582 dataset was based on GPL16956 (Agilent-045997 Arraystar human lncRNA microarray V3).…”

“…Then, we set a threshold that lncRNAs with logFC > 4 would be retained for lncRNA-miRNA interaction. Due to lack of miRNA expression pro ling data, we searched HMDD v3.2 [22] database (http://www.cuilab.cn/hmdd) for LVNC related miRNAs and supplemented with document retrieval [14,15]. Based on both experimental evidence and software prediction, DIANA-LncBase V3 [23] database (https://diana.e-ce.uth.gr/lncbasev3/home) was involved to predict lncRNA-miRNA interaction.…”

“…Mitochondrial DNA genes encoding for rRNAs and tRNAs were reported in association with LVNC [13]. Recently, two studies respectively reported LVNC related miRNAs [14] and lncRNAs [15] for the rst time, revealing a new dimension for LVNC investigation. The analysis procedures were described in Fig.…”