Abstract
Purpose :
Long-coding RNAs (IncRNAs) have potential to develop diagnostic markers or therapeutic targets given their wide function in biological regulation. This study aimed to identify differentially expressed IncRNAs in Fuch’s Endothelial Cell Dystrophy (FECD) RNA-seq datasets to gain some insights into the molecular mechanisms underlying this condition.
Methods :
RNA-seq datasets from GEO (GSE101872) were analyzed: two healthy controls and five FECD samples. We mapped reads to the human reference genome (hg38). Transcripts were assembled and quantified using the most recent GENCODE annotation (release 29). 19940 protein-coding genes and 16066 lncRNA genes were queried. Gene expression matrices were generated as Fragments Per Kilobase of transcript per Million mapped reads (FPKM) and as normalized counts. Analysis of differential gene expression was performed through pairwise comparisons using normalized counts. Expressed genes (FPKM > 1) with fold-change > 2 and p-value < 0.05 were considered to be differentially expressed (DE). In order to make some inferences about the functions of upregulated DE genes, we performed a gene ontology (GO) enrichment analysis using a hypergeometric test with GO terms. To infer the functions of DE lncRNA, we adopted a guilt-by-association method.
Results :
A total of 450 protein-coding genes and 27 lncRNA genes were upregulated in FECD condition. Among the top enriched pathways related to the up-regulated genes were interferon signaling, adaptative immune system, and interferon gamma signaling. Similarly, 88 protein-coding and 12 lncRNA genes were downregulated in FECD samples. The top pathways related to these genes were RUNX1 (that regulates expression of components of tight junctions), potassium transport channels, and assembly of collagen fibrils. The guilt-by-association method revealed that lncRNAs are involved in functions related to the progression of FECD. By analyzing the genomic location of lncRNAs and their correlation in expression with DE protein-coding genes, we were able to pinpoint lncRNA candidate transcripts potentially involved in the regulation of FECD condition.
Conclusions :
There are IncRNAs associated with FECD. This study provides a catalogue of lncRNAs potentially involved in the regulation and progression of FECD, which may be used as therapeutic targets.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.