LncRNA GAS5 relates to Th17 cells and serves as a potential biomarker for sepsis inflammation, organ dysfunctions and mortality risk

Abstract

Background Long noncoding RNA GAS5 (lnc‐GAS5) is able to regulate macrophage M1 polarization and Th17 cell differentiation, also engaged in sepsis‐induced inflammation and organ injury. This study aimed to further evaluate its linkage with Th1 cells and Th17 cells, as well as its clinical value in sepsis management. Methods About 101 sepsis patients were enrolled followed by peripheral blood mononuclear cell (PBMC) and serum samples collection. PBMC lnc‐GAS5 was detected by RT‐qPCR; Th1 cells and Th17 cells in PBMC CD4+ T cells were detected by flow cytometry; serum IFN‐γ and IL‐17A were detected by ELISA. Besides, PBMC lnc‐GAS5 was also detected in 50 health controls (HCs). Results Lnc‐GAS5 was reduced in sepsis patients than in HCs (p < 0.001), which also well‐distinguished sepsis patients from HCs with AUC 0.860. Lnc‐GAS5 did not relate to Th1 cells (p = 0.059) or IFN‐γ (p = 0.192); while negatively linked with Th17 cells (p = 0.002) and IL‐17A (p = 0.019) in sepsis patients. Interestingly, lnc‐GAS5 negatively correlated with SOFA score (p = 0.001), SOFA‐Respiratory system score (p = 0.001), SOFA‐Coagulation score (p = 0.015), and SOFA‐Renal system score (p = 0.026), but not SOFA‐Liver score (p = 0.080), SOFA‐Cardiovascular system score (p = 0.207) or SOFA‐Nervous system score (p = 0.182) in sepsis patients. Furthermore, lnc‐GAS5 was negatively related to CRP (p = 0.002) and APACHE II score (p = 0.004) in sepsis patients. Finally, lnc‐GAS5 was decreased in dead sepsis patients compared to survivors (p = 0.007), which also distinguished sepsis deaths from survivors with AUC 0.713. Conclusion Lnc‐GAS5 relates to Th17 cells and serves as a potential biomarker for sepsis severity and mortality risk.

Regulatory Effects of Long Non-coding RNAs on Th17/Treg Differentiation and Imbalance

“…42 Low expression of GAS5 in patients with sepsis is negatively correlated with Th17 and IL-17A, and possibly has an inhibitory effect on the inhibition of Th17 cell differentiation. 43 It was also observed that GAS5 expression declined in the PBMCs of immune thrombocytopenia (ITP). Increased GAS5 expression alleviates ITP through TRAF6-mediated degradation of STAT3, inhibiting Th17 differentiation.…”

The Role of Transcriptomics in Redefining Critical Illness

“…miR-150 is a well-investigated miRNA that can discriminate between sepsis and non-infectious systemic inflammatory response syndrome (SIRS) [ 23 ]. The lncRNA GAS5 displays prognostic potential in predicting 28-day mortality risk in septic patients [ 24 ]. Although far from exhaustive, these individual RNAs reflect the wide-ranging potential of transcriptomics in deriving novel biomarkers for diagnosis and prognostic enrichment.…”

“…The lncRNA GAS5 displays prognostic potential in predicting 28-day mortality risk in septic patients [24]. Although far from exhaustive, these individual RNAs reflect the wide-ranging potential of transcriptomics in deriving novel biomarkers for diagnosis and prognostic enrichment.…”

The Common LncRNAs of Neuroinflammation-Related Diseases

“…(Liu et al, 2018) As a biomarker, GAS5 is related to the risk of gastric cancer, uterine cervical cancer, and prostate cancer, and is also a potential marker of sepsis inflammation. (Dong et al, 2020;Lin et al, 2019;Weng et al, 2020;Zhang et al, 2022b) Associated with miR-21 and miR-140 as potential markers of allergic rhinitis. (Song et al, 2021) As far as current studies are concerned, GAS5 is up-regulated in neurosystemic diseases and plays a proinflammatory role in neuroinflammation.…”