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 r… Show more
“…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).…”
Preeclampsia is a lethal pregnancy specific hypertensive disorder involving multisystem. Despite extensive studies to investigate the causes of preeclampsia, the pathogenesis still remains largely unknown. Long non-coding RNAs (lncRNAs) are a diverse class of non-translated RNAs which play a crucial part in various biological phenomena. Although lncRNA Growth Arrest-Specific 5 (GAS5) aberrantly expressed in multiple cancer tissues and is implicated in multiple biological processes of tumor cells, little is known about its role in preeclampsia. In this study, 40 patients with preeclampsia and 32 gestational age matched normotension pregnant women were recruited. Using quantitative real-time polymerase chain reaction (qRT-PCR), we found higher expression of GAS5 in placenta of preclamsia affected women. The level of GAS5 existed strongly in correlation with Thrombin Time indicating coagulation function and other clinical parameters by Pearson correlation analysis. Then we constructed the GAS5 lentivirus expression vectors and transfected into human trophoblast cell lines HTR-8/SVneo and JEG-3. Using in vitro cell culture studies, we found an inhibited effect of GAS5 on proliferative ability, migratory ability and invasive ability however; no effect on apoptosis was detected. Further mechanistic analysis found that GAS5 modulated microRNA-21 (miR-21) in an opposite variation tendency by qRT-PCR and rescue experiment. In addition, inhibition of GAS5 promoted the activation of PI3K/AKT signaling pathway and its downstream proteins covering MMP-9 and TP53 as evident from our qRT-PCR and western blot analyses. Thus, we suggested that GAS5 might involve in pregnancy with preeclampsia by influencing the biological functions of trophoblast cells through the regulation of miR-21 and activation of PI3K/AKT signaling pathway and its downstream targets, which may contribute to reveal the nature of preeclampsia.
“…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).…”
Preeclampsia is a lethal pregnancy specific hypertensive disorder involving multisystem. Despite extensive studies to investigate the causes of preeclampsia, the pathogenesis still remains largely unknown. Long non-coding RNAs (lncRNAs) are a diverse class of non-translated RNAs which play a crucial part in various biological phenomena. Although lncRNA Growth Arrest-Specific 5 (GAS5) aberrantly expressed in multiple cancer tissues and is implicated in multiple biological processes of tumor cells, little is known about its role in preeclampsia. In this study, 40 patients with preeclampsia and 32 gestational age matched normotension pregnant women were recruited. Using quantitative real-time polymerase chain reaction (qRT-PCR), we found higher expression of GAS5 in placenta of preclamsia affected women. The level of GAS5 existed strongly in correlation with Thrombin Time indicating coagulation function and other clinical parameters by Pearson correlation analysis. Then we constructed the GAS5 lentivirus expression vectors and transfected into human trophoblast cell lines HTR-8/SVneo and JEG-3. Using in vitro cell culture studies, we found an inhibited effect of GAS5 on proliferative ability, migratory ability and invasive ability however; no effect on apoptosis was detected. Further mechanistic analysis found that GAS5 modulated microRNA-21 (miR-21) in an opposite variation tendency by qRT-PCR and rescue experiment. In addition, inhibition of GAS5 promoted the activation of PI3K/AKT signaling pathway and its downstream proteins covering MMP-9 and TP53 as evident from our qRT-PCR and western blot analyses. Thus, we suggested that GAS5 might involve in pregnancy with preeclampsia by influencing the biological functions of trophoblast cells through the regulation of miR-21 and activation of PI3K/AKT signaling pathway and its downstream targets, which may contribute to reveal the nature of preeclampsia.
“…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).…”
Section: Ncrnas Regulate the Aberrant Differentiation Of Cd4 + T Subsmentioning
Non-coding RNAs (ncRNAs) are indispensable for CD4 + T cell differentiation and functions. By directly or indirectly regulating immune gene expression, ncRNAs give flexible instructions to guide the biological processes of CD4 + T cells and play a vital role in maintaining immune homeostasis. However, the dysfunction of ncRNAs alters the gene expression profiles, disturbs the normal biological processes of CD4 + T cells, and leads to the functional changes of CD4 + T cells, which is an underlying cause of systemic lupus erythematosus (SLE). In this review, we focus on the recent advances in the roles of ncRNAs in CD4 + T cell functions and differentiation, as well as their potential applications in the diagnosis and treatment of SLE.
“…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].…”
Section: Lncrnas That May Specifically Identify Sle Patientsmentioning
confidence: 99%
“…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.…”
Section: Lncrnas That May Specifically Identify Sle Patientsmentioning
Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE). LN often leads to kidney failure, affecting the quality of a patient's life. There are several classical biomarkers that assist nephrologists' daily practice. For more than 50 years, anti-double stranded DNA antibodies and complement components C3 and C4 have been used for LN disease activity evaluation. The major obstacle in the usage of conventional biomarkers is that none of them have both high specificity and high sensitivity. Moreover, an invasive kidney biopsy is still the gold standard for renal involvement detection in SLE patients. Therefore, new non-invasive biomarkers are needed for the early and accurate establishment of LN. Among the promising candidates are long non-coding RNAs (lncRNAs). Their dysregulation appears to have predictive and diagnostic potential. Furthermore, these biomarkers like other conventional biomarkers give insight into the pathogenesis of LN. This review aims to summarize the available information on lncRNAs in SLE patients and to present their future opportunities to add to the conventional biomarkers in the diagnosis and monitoring of LN.
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