Background: Non-coding RNA has been shown to participate in numerous biological and pathological processes and has attracted increasing attention in recent years. Recent studies have demonstrated that long non-coding RNA and micro RNA can interact through various mechanisms to regulate mRNA. Yet the gene-gene interaction has not been investigated in coronary heart disease (CHD).
Methods: High throughput sequencing were used to identify differentially expressed (DE) lncRNA, miRNA, and mRNA profiles between CHD and healthy control. Gene Oncology (GO), KEGG enrichment analysis were performed. Gene-gene interaction network were constructed and pivotal genes were screened out. Lentivirus-induced shRNA infection and qRT-PCR were performed to validated the gene-gene interactions.
Results: A total of 62 lncRNAs, 332 miRNAs and 366 mRNAs were differentially expressed between CHD and healthy control. GO and KEGG analysis show that immune related molecular mechanisms and biological processes play a role in CHD. The gene-gene interaction network were constructed and visualized based on Pearson correlation coefficients and starBase database. 6 miRNAs in the network were significantly correlated to left ventricular ejection fraction, total choleterol and homocysteine. 2 lncRNAs (CTA-384D8.35 and CTB-114C7.4 (refseq entry LOC100128059)), 1 miRNA (miR-4497), and 1 mRNA (NR4A1) were the pivotal genes. Lentivirus-induced shRNA infection and qRT-PCR had validated the pivotal gene-gene interactions.
Conclusions: These results have shown the potential of lncRNA, miRNA, and mRNA as clinical biomarkers and in elucidating pathological mechanisms of CHD from a transcriptomic perspective.
Keywords: Coronary heart disease; Interaction network; Long non-coding RNA; Micro RNA; Transcriptome sequencing.