Dysregulated lncRNAs are Involved in the Progress of Sepsis by Constructing Regulatory Networks in Whole Blood Cells

Abstract

Sepsis is a highly heterogeneous syndrome that is caused by an unbalanced host response to an infection. Long noncoding RNAs (lncRNAs) have been reported to exert regulatory roles in a variety of biological processes, and became potential biomarkers and therapeutic targets for diverse diseases. However, current understanding on the roles of lncRNAs in sepsis is extremely limited. Herein, to decipher the underlying functions of lncRNAs, we reexplored the 83 transcriptome datasets from specimens with sepsis, no_sepsis by final diagnosis, and control. The results of differentially expressed genes (DEGs), differentially expressed lncRNA (DElncRNA) analysis, and co-expression analysis of lncRNA–mRNA pairs were obtained. We found that the expression pattern of lncRNAs was significantly activated in sepsis specimens, which was clearly distinguished in sepsis from no_sepsis and control specimens. By performing co-expression analysis, we found DElncRNAs were closely related to T-cell activation and immune response–related terms in sepsis by regulating mRNA expression in the trans manner. The lncRNA–mRNA network and the qRT-PCR test revealed that lncRNAs LINC00861, RP11-284N8.3, and CTB-61M7.2 were significantly correlated with the pathogenesis of sepsis. In addition, weighted gene co-expression analysis (WGCNA) and cis-regulation analysis also revealed sepsis-specific lncRNAs were highly associated with important biological processes correlated with sepsis. In summary, the systematic dysregulation of lncRNAs is tightly involved in the remodeling of gene expression regulatory network in sepsis, and the lncRNA–mRNA expression network may be used to refine biomarker predictions for developing novel therapeutic approaches in sepsis.

The ability of long non-coding RNA RP11-284N8.3 to predict the risk, the severity and 28-day mortality of adults with sepsis

“…lncRNAs have been demonstrated to exert key regulatory roles in all sorts of biological processes, thereby contributing to the development and progression of diverse diseases, including sepsis. [ 18 , 19 ] In our prior study, [ 17 ] we profiled the differentially expressed lncRNAs and mRNAs co-expression network in sepsis based on a publicly available RNA-seq data, and identified 3 sepsis specific lncRNAs, including RP11-284N8.3, CTB-61M7.2, and LINC00861. Among of them, lncRNA RP11-284N8.3 is entirely unknown to sepsis and may primarily participate in T cell activation and immune response based on the functional enrichment analysis of its highly co-expressed mRNAs.…”

“…[7][8][9][10][11] With the advance of high throughput sequencing technology, an increasing number of sepsis-associated lncRNAs had been identified. [12][13][14][15][16] In our prior study, [17] the lncRNA-mRNA network in sepsis was constructed based on a publicly available RNA-seq data, and we identified a potential key sepsis-associated lncRNA RP11-284N8.3. At present, lncRNA RP11-284N8.3 is largely with unknown functions in sepsis.…”

RNA-Binding Proteins and Alternative Splicing Genes Are Coregulated in Human Retinal Endothelial Cells Treated with High Glucose

“…The ASEs and regulated alternative splicing events (RASEs) between the samples were defined and quantified using the ABLas pipeline as described previously [ 27 , 28 ]. In brief, ABLas detection of ten types of ASEs was based on the splice junction reads, including exon skipping (ES), alternative 5′ splice site (A5SS), alternative 3′ splice site (A3SS), intron retention (IR), mutually exclusive exons (MXE), mutually exclusive 5′ UTRs (5pMXE), mutually exclusive 3′ UTRs (3pMXE), cassette exon, A3SS&ES, and A5SS&ES [ 29 ].…”

Genome-wide investigation of lncRNAs revealed their tight association with gastric cancer

“…Recent research has increasingly concentrated on the significance of non-coding RNAs (ncRNAs) in the context of GC. These RNA molecules, which cannot be directly converted into proteins within cells, exert a vital role in various cellular processes, such as modulation of gene expression (Cheng et al 2021 ). The main types of these ncRNAs include microRNA (miRNA), circular RNA(circRNA), and long-chain non-coding RNA(lncRNA) (Lee et al 2019 ), among which lncRNA is defined as a transcription product with a length of more than 200 nucleotides.…”