Association of long non‑coding RNA GAS5 and miR‑21 levels in CD4+ T cells with clinical features of systemic lupus erythematosus

Abstract

Abstract. The present study aimed to assess the expression of growth arrest-specific 5 (GAS5) and microRNA (miR)-21 in systemic lupus erythematosus (SLE), and attempted to explore their association with clinical features. CD4 + T cells were isolated from peripheral blood of healthy donors and SLE patients by magnetic-activated cell sorting. GAS5 and miR-21 expression levels in cluster of differentiation (CD)4 + T cells were measured by reverse-transcription quantitative polymerase chain reaction. The results revealed that GAS5 and miR-21 levels were significantly elevated in CD4 + T cells of patients with SLE compared with those in control subjects (P<0.05). Regarding clinical features, SLE patients with ulceration had higher GAS5 expression levels in CD4 + T cells than those without ulceration (P<0.05), and the expression of miR-21 was significantly higher in CD4 + T cells of SLE patients with low levels of complement component 3 (C3) than in those with normal levels of complement C3 (P<0.05).In conclusion, GAS5 and miR-21 in CD4 + T cells may serve as potential biomarkers for the diagnosis and monitoring of the progression of SLE. IntroductionSystemic lu pus erythematosus (SLE) is a multisystemic, chronic inflammatory autoimmune disease of unknown etiology. It is characterized by various pathogenic autoantibodies and immune complexes as well as damage to multiple organ systems, and the course of SLE is long followed by remission and acute attack. The prevalence varies from 31-70/100,000 individuals in China and from 20-70/100,000 individuals worldwide. It is sex-associated, occurring nine times more often in women than in men, particularly in women of child-bearing age (15-35 years) (1-3). The interaction between certain genetic and environmental factors, including chemical factors, viruses and drugs, damages normal immune tolerance and contributes to SLE. Dysfunctional T cells interact with new antigens constantly, leading to a persistent autoimmune reaction (4,5). Previous studies have confirmed that the abnormal activation and proliferation of self-reactive cluster of differentiation (CD)4 + T lymphocytes have a central role in SLE. CD4 + T cells interact with antigen-specific B cells, to make the latter ones become more effective and produce autoantibodies. In addition, CD4 + T cells produce various cytokines when they are activated, which may engender inflammatory reactions (6,7).Long non-coding RNAs (lncRNAs) are a class of non-protein-coding RNA with transcripts longer than 200 nucleotides. They have numerous important biological functions through different molecular mechanisms, and are closely associated with a variety of clinical diseases, including tumors, metabolic disease and autoimmune diseases. Growth arrest-specific 5 (GAS5), a non-coding gene that hosts a number of small nucleolar RNAs, has been suggested to have numerous important roles in apoptosis and cell growth inhibition. Previous studies have reported that human GAS5 was upregulated in osteoarthritis (OA) patients (8) and downregulated i...

Long Non-coding RNA Gas5 Is Associated With Preeclampsia and Regulates Biological Behaviors of Trophoblast via MicroRNA-21

“…GAS5 can act as the molecular spongy binding numerous microRNAs mutually but the observations in detail are still remained largely unclear. Negative regulation between GAS5 and microRNA-21 (miR-21) has been certificated in various tumors and other diseases for the GAS5 Exon 4 contains miR-21 binding sequence (Zhang et al, 2013;Song et al, 2014;Hu et al, 2016;Cao et al, 2017;Tao et al, 2017;Suo et al, 2018;Yao et al, 2019).…”

Non-Coding RNAs in CD4+ T Cells: New Insights Into the Pathogenesis of Systemic Lupus Erythematosus

“…Silencing miR-21 with a tiny seed-targeting LNA alleviates splenomegaly in B6.Sle123 mice and decreases the expression of PDCD4 and the population of Fas receptorexpressing lymphocytes (115). In SLE patients, the expression of miR-21 positively correlates with the disease activity and negatively correlates with the levels of C3 and IL-2, while the expression of miR-31 decreases and positively correlates with IL-2 production (116,117). And IL-2 deficiency is responsible for the compromised suppressor ability of Treg cells in SLE (118).…”

Long Non-Coding RNAs as New Biomarkers in Lupus Nephritis: A Connection Between Present and Future

“…Their regulation and association with some clinical markers of the disease are shown in Table 2. LncRNA growth arrest-specific transcript 5 (GAS5) is aberrantly expressed in SLE patients when compared with healthy controls [35][36][37][38]. GAS5 levels are significantly lower in patients with active SLE and are negatively correlated with the SLE disease activity index (SLEDAI) score, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) [35,36].…”

“…GAS5 levels are significantly lower in patients with active SLE and are negatively correlated with the SLE disease activity index (SLEDAI) score, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) [35,36]. The CD4+ T cells of SLE patients with ulcerations have a high expression of GAS5 [38]. Since GAS5 is overexpressed in an immune cell, probably it has specific functions in autoimmune diseases such as SLE.…”