Expression Of lncRNA XIST Research Articles

Diagnostic Value of lncRNA XIST in Saliva for Early Peri-Implantitis.

To analyse the relative expression and diagnostic potential of lncRNA XIST (XIST) in peri-implantitis, and explore the related mechanism of XIST in peri-implantitis. XIST expression in saliva of patients with peri-implantitis was detected by qRT-PCR. The diagnostic significance of XIST in peri-implantitis was assessed by ROC curve. Clinical indicators of the included patients were collected and the correlation between XIST levels and peri-implant indicators was determined by Pearson correlation analysis. Bioinformatic prediction and luciferase reporter assay confirmed the targeting relationship of XIST with downstream factors. Salivary XIST levels were obviously higher in patients with peri-implantitis than in the healthy control group, and the AUC value for identifying patients was 0.8742 with a sensitivity and specificity of 83.5% and 81.4%. Patients in the peri-implantitis group had higher levels of plaque index (PLI), sulcus bleeding index (SBI) and probing depth (PD) than those in the healthy control group, and the expression of XIST was positively correlated with PLI, SBI, and PD levels. In addition, miR-150-5p was confirmed to be a potential downstream target of XIST. XIST was overexpressed in the saliva of patients with peri-implantitis and correlated with the severity of the disease. XIST has high diagnostic significance for detecting peri-implantitis.

Clinical significance of lncRNA XIST expression in cholangiocarcinoma and its effect on cell migration and invasion

BackgroundCholangiocarcinoma is a malignant tumor that occurs in the bile duct system, and the prognosis of patients is poor. Currently, research suggests that long non-coding RNAs (lncRNAs) in the treatment and prevention of cholangiocarcinoma. This study primarily focuses on the regulation and potential mechanism of the lncRNA XIST (XIST) in cholangiocarcinoma. MethodsThe levels of XIST and miR-126–3p in cholangiocarcinoma tissues and cells were detected using real-time quantitative polymerase chain reaction (RT-qPCR). Cell transfection status, including migration and invasion, was examined via the Transwell method. The relationship between XIST and miR-126–3p was observed by dual-luciferase gene reporter assay and verified by rescue assays. Additionally, the prognostic significance of XIST in cholangiocarcinoma was determined using Kaplan-Meier and multivariate Cox regression analyses. ResultsXIST expression was increased in cholangiocarcinoma, while miR-126–3p was decreased, in both tissues and cells. The successful construction of silencing XIST was found to inhibit the count of cell migration and invasion. XIST directly targeted miR-126–3p to regulate the progression of cholangiocarcinoma. ConclusionXIST sponging miR-126–3p inhibited the progression of cholangiocarcinoma and improved the prognosis for patients. This finding provides new insights and opportunities for future studies on cholangiocarcinoma prognostic biomarkers.

Circulating long noncoding RNA, Zfpm2-As1, and XIST based on medical data analysis are potential plasma biomarkers for gastric cancer diagnosis.

Long noncoding RNAs (lncRNAs) participate in diseases, especially tumorigenesis, including gastric cancer (GC). Although lncRNAs in GC tissues have been extensively studied in previous research, the possible significance of circulating lncRNAs in diagnosing GC is still unknown. The present work investigated lncRNAs ZFPM2-AS1 and XIST with high expression in GC tissues proved as potential plasma biomarkers from 20 early GC cases, 100 GC cases, and 90 normal subjects. The possible correlation between ZFPM2-AS1 and XIST expression levels was analyzed with general characteristics and clinicopathological features. The performance in diagnosis was assessed according to receiver operating characteristic (ROC) analysis. According to the results, XIST and ZFPM2-AS1 expression remarkably increased within GC plasma relative to normal subjects (P< 0.01); besides, lncRNA XIST expression after surgery had a tendency of downregulation compared with preoperative levels (P< 0.05). Moreover, the area under ROC curve (AUC) values were 0.62 for ZFPM2-AS1 and 0.68 for XIST, while the pooled AUC value of CA-724 and two lncRNAs was 0.751. Circulating lncRNAs ZFPM2-AS1 and XIST can serve as the candidate plasma biomarkers used to diagnose GC.

Polysaccharides from Dendrobium officinale delay diabetic kidney disease interstitial fibrosis through LncRNA XIST/TGF-β1

PurposeRenal interstitial fibrosis is a pathological manifestation of the progression of diabetic kidney disease (DKD). Dendrobium officinale polysaccharides (DOP), one of the major active components of Dendrobium officinale, have hypoglycemic and hypolipidemic effects and are used clinically to treat diabetes. However, the role of DOP in delaying DKD progression remains unclear. This study aimed to explore the potential mechanisms by which DOP delays DKD renal interstitial fibrosis. MethodsUsing db/db mice as a model of DKD, we administered DOP by gavage and observed its therapeutic effectiveness. Employing ASO technology, we knocked down lncRNA XIST expression in kidney tissues and detected the expression of lncRNA XIST, TGF-β1, and renal interstitial fibrosis-related molecules. ResultsDOP was primarily composed of monosaccharides, with 91.57% glucose and 1.41% mannose, forming a spheroid-like structure. It has a high polydispersity index with an Mw/Mn of 6.146, and the polysaccharides are mainly connected by 4-Man(p) and 4-Glc(p) linkages. In the kidneys of db/db mice, lncRNA XIST and TGF-β1 are highly expressed; however, their expression is significantly reduced after gastric infusion with DOP, and upon knockdown of lncRNA XIST, it might delay the progression of renal interstitial fibrosis in DKD. ConclusionDOP may delay the progression of DKD renal interstitial fibrosis through the regulation of the LncRNA XIST/TGF-β1 related fibrotic pathway. This provides a new perspective for clinical strategies to delay the progression of DKD renal interstitial fibrosis.

LncRNA XIST Protects Against Polycystic Ovary Syndrome via the Regulation of miR-212-3p/RASA1 Axis.

The polycystic ovary syndrome (PCOS), a common endocrine disorder, is mainly related to infertility. Moreover, it is characterized by promoted androgen, suppressed ovulation and insulin resistance. Long non-coding RNA X inactive specific transcript (lncRNA XIST), known as an oncogene or a cancer inhabited factor, is involved in several disease. However, the diagnostic mechanisms of lncRNA XIST in PCOS have not been clarified. Our study aimed to explain whether lncRNA XIST regulates KGN cells proliferation and apoptosis via microRNA (miR)-212-3p/RASA1 axis in PCOS. Levels of lncRNA XIST, miR-212-3p and RASA1 in KGN cells were detected through reverse transcription quantitative polymerase chain reaction (RT-qPCR) assay. Fluorescence in situ Hybridization (FISH) was performed to confirm the expression of lncRNA XIST and miR-212-3p in KGN cells. StarBase and dual-luciferase reporter assay were applied for exploring the interaction between miR-212-3p and RASA1. Cell viability, apoptosis, protein expression of Bcl-2 and Bax were assessed by MTT, flow cytometry analysis, RT-qPCR and western blot, respectively. We found that lncRNA XIST was low-expressed, miR-212-3p was over-expressed, and RASA1 was dramatically down-regulated in KGN cells. LncRNA XIST negatively regulated miR-212-3p expression in KGN cells. MiR-212-3p interacted with RASA1 and negatively regulated RASA1 levels in KGN cells. Up-regulation of lncRNA XIST signally decreased cells viability, stimulated more apoptotic cells, enhanced Bax expression, and depressed Bcl-2 level in KGN cells. However, these observations were abolished after miR-212-3p mimic treatment. Furthermore, miR-212-3p inhibitor significantly inhibited cell proliferation, enhanced more apoptotic cells, increased Bax expression, and decreased Bcl-2 level in KGN cells, and these effects were eliminated by RASA1-siRNA transfection. Our observations revealed that lncRNA XIST protects against PCOS through regulating miR-212-3p/RASA1 axis, suggesting that lncRNA XIST may be a promising therapeutic target for PCOS therapy.

Inhibition of Mir-21-5p Affects the Expression of LNCRNA X-Inactive Specific Transcript and Induces Apoptosis in MCF-7 Breast Cancer Cells.

We aimed to investigate miR-21-5p inhibition effect on lncRNA-XIST expression and apoptosis status of MCF-7 cells. The MCF-7 cells were cultured and transfected by the anti-miR-21-5p oligonucleotide and expression of miR-21-5p, lncRNA-XIST, apoptosis-associated genes (bax and p53) and one miR-21-5p-unrelated lncRNA (BC200) was assessed by RT-qPCR. Furthermore, cell viability checked by MTT assay and apoptosis and cell cycle in transfected cells were detected by flow cytometry. Also, bioinformatics analysis on the transcriptome data confirmed that the lncRNA XIST might have a critical role in breast cancer (BC) cell apoptosis through ceRNAs mechanism and possible regulatory interactions with miR-21-5p. Expression of miR-21-5p and lncRNA-XIST was significantly down- and up-regulated respectively (P<0.05). However, there was no significant change in lncRNA-BC200 expression. Also, the expression of bax and p53 upraised significantly (P<0.05). In transfected cells, MTT and flow cytometry assays reported a highly significant decrease and increase in viability and apoptosis respectively. Inhibition of miR-21-5p resulted in significant upregulation of lncRNA-XIST and apoptosis-associated genes bax and p53, which led to the induction of apoptosis in MCF-7 cells. Therefore, more investigations may provide a valuable target for studies on molecular therapies for BC.

LncRNA XIST promotes bladder cancer progression by modulating miR-129-5p/TNFSF10 axis

BackgroundThe differential expression, biological function, and ceRNA regulatory mechanism of lncRNA XIST in bladder cancer (BC) were investigated, and its clinical values for the early diagnosis of bladder cancer patients were elucidated.MethodsqRT-PCR was employed to detect the expression patterns of lncRNA XIST, miR-129-5p and TNFSF10. The biological functions were measured by CCK8 assay, wound healing assay and transwell assay. Bioinformatics analysis and Dual-Luciferase reporter assay were employed to evaluate the interactions between the lncRNA XIST, miR-129-5p and TNFSF10.ResultsLncRNA XIST and TNFSF10 were highly expressed and miR-129-5p was low expressed (P < 0.05) in bladder cancer cell line. The depletion of lncRNA XIST inhibited BC proliferation, migration and invasion. Mechanistically, lncRNA XIST could sponge miR-129-5p to regulate TNFSF10 expression in bladder cancer. Furthermore, compared with adjacent tissues, lncRNA XIST and miR-129-5p were lowly expressed (P < 0.01) in bladder cancer tissues, and TNFSF10 was highly expressed (P < 0.001). miR-129-5p and TNFSF10 were associated with the risk of bladder cancer (P < 0.05); the difference in AUC values for the diagnosis of bladder cancer by lncRNA XIST (AUC = 0.739), miR-129-5p (AUC = 0.850) and TNFSF10 (AUC = 0.753) was statistically significant (P < 0.01), and the three genes combined AUC was 0.900, 95%CI was 0.842–0.958 with a sensitivity of 83.3% and specificity of 86.7%.ConclusionXIST, an elevated lncRNA in bladder cancer, inhibition of which could suppress the progression of BC. LncRNA XIST and miR-129-5p could form ceRNA to regulate the expression of TNFSF10.

Long noncoding RNA XIST promotes cell proliferation and migration in diabetic foot ulcers through the miR-126-3p/EGFR axis

BackgroundThe prevalence of diabetic foot ulcers (DFUs) has caused serious harm to human health. To date, a highly effective treatment is lacking. Long noncoding RNA X-inactive specific transcript (lncRNA XIST) has been the subject of mounting research studies, all of which have found that it serves as a protective factor against certain diseases; however, its function in DFUs is not entirely understood. This study was performed to determine the importance of the lncRNA XIST in the pathogenesis and biological function of DFUs.MethodsDiabetic ulcer skin from rats was analysed using haematoxylin-eosin (HE), Masson’s trichrome, and immunohistochemistry (IHC) staining. The differences in the expression of genes and proteins were examined with real-time quantitative polymerase chain reaction (RT–qPCR) and Western blotting. Next, the interaction was verified with a dual luciferase gene reporter assay. In addition, CCK-8, Transwell, and wound healing assays were used to assess the proliferation and migration of HaCaT cells.ResultsThe lncRNA XIST and epidermal growth factor receptor (EGFR) were downregulated, while microRNA-126-3p (miR-126-3p) was increased in diabetic ulcer rat skin tissues and high glucose-induced HaCaT cells. In addition, we found that the lncRNA XIST binds to miR-126-3p and that EGFR is directly targeted by miR‑126‑3p. Silencing XIST contributed to upregulated miR-126-3p expression, thus lowering EGFR levels and inhibiting the proliferative and migratory abilities of high glucose-treated HaCaT cells; however, the miR-126-3p inhibitor and overexpression of EGFR reversed this effect.ConclusionDecreased lncRNA XIST expression inhibits the proliferative and migratory abilities of high glucose-induced HaCaT cells by modulating the miR-126-3p/EGFR axis, causing delayed wound healing.

Effect of lncRNA XIST on acute myeloid leukemia cells via miR-142-5p-PFKP axis

ABSTRACT Acute myeloid leukemia (AML) is the common blood cancer in hematopoietic system-related diseases and has a poor prognosis. Studies have shown that long non-coding RNAs (lncRNAs) are closely related to the pathogenesis of a variety of diseases, including AML. However, the specific molecular mechanism remains unclear. Hence, the objective of this study was to investigate the effect and mechanism of lncRNA X inactive specific transcript (lncRNA XIST) on AML. To achieve our objective, some tests were performed. Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to detect the expression of lncRNA XIST, miR-142-5p and the platelet isoform of phosphofructokinase (PFKP). The targeting relationship between miR-142-5p and lncRNA XIST and PFKP was verified by Pearson correlation analysis, dual-luciferase reporter assay, and pull-down assay. Functional experiments were used to analyze the effect and mechanism of action of knocking down lncRNA XIST on THP-1 and U937 cells. Compared with bone marrow cells, lncRNA XIST and PFKP expression levels were up-regulated and miR-142-5p expression levels were down-regulated in AML. Further analysis revealed that lncRNA XIST targeted and bound to miR-142-5p, and PFKP was a target gene of miR-142-5p. Knockdown of lncRNA XIST significantly promoted miR-142-5p expression to down-regulate PFKP in THP-1 and U937 cells, while the cell proliferation, cell viability, and cell cycle arrest were inhibited and apoptosis was increased. Knockdown of miR-142-5p reversed the functional impact of lncRNA XIST knockdown on AML cells. In conclusion, down-regulation of lncRNA XIST can affect the progression of AML by regulating miR-142-5p.

LncRNA xist regulates sepsis associated neuroinflammation in the periventricular white matter of CLP rats by miR-122-5p/PKCη Axis.

Neuroinflammation is a common feature of many neurological diseases, and remains crucial for disease progression and prognosis. Activation of microglia and astrocytes can lead to neuroinflammation. However, little is known about the role of lncRNA xist and miR-122-5p in the pathogenesis of sepsis-associated neuroinflammation (SAN). This study aims to investigate the role of lncRNA xist and miR-122-5p in the pathogenesis of SAN. Levels of miR-122-5p and proinflammatory mediators were detected in the cerebrospinal fluid (CSF) of patients with intracranial infection (ICI) by ELISA and qRT-PCR. miRNA expression in the periventricular white matter (PWM) in rats was analyzed by high-throughput sequencing. Levels of lncRNA xist, miR-122-5p and proinflammatory mediators in the PWM were measured using qRT-PCR and western blot. Bioinformatics analysis was used to predict the upstream and downstream of miR-122-5p. The interaction between miR-122-5p and its target protein was validated using luciferase reporter assay. BV2 and astrocytes were used to detect the expression of lncRNA xist, miR-122-5p. The level of miR-122-5p was significantly decreased in the CSF of ICI patients, while the expression of IL-1β and TNF-α were significantly upregulated. Furthermore, it was found that the expression of IL-1β and TNF-α were negatively correlated with the level of miR-122-5p. A high-throughput sequencing analysis showed that miR-122-5p expression was downregulated with 1.5-fold changes in the PWM of CLP rats compared with sham group. Bioinformatics analysis found that lncRNA xist and PKCη were the upstream and downstream target genes of miR-122-5p, respectively. The identified lncRNA xist and PKCη were significantly increased in the PWM of CLP rats. Overexpression of miR-122-5p or knockdown of lncRNA xist could significantly downregulate the level of PKCη and proinflammatory mediators from activated microglia and astrocytes. Meanwhile, in vitro investigation showed that silencing lncRNA xist or PKCη or enhancing the expression of miR-122-5p could obviously inhibit the release of proinflammatory mediators in activated BV2 cells and astrocytes. LncRNA xist could regulate microglia and astrocytes activation in the PWM of CLP rats via miR-122-5p/PKCη axis, further mediating sepsis associated neuroinflammation.

High Expression of LncRNA XIST as an Index Helping to Diagnose Parkinson’s Disease

High Expression of LncRNA XIST as an Index Helping to Diagnose Parkinson’s Disease

Prevalence of Diabetic Kidney Disease with Different Subtypes in Hospitalized Patients with Diabetes and Correlation Between eGFR and LncRNA XIST Expression in PBMCs.

Diabetic kidney disease (DKD) has become the leading cause of end-stage kidney disease (ESKD) in most countries. Recently, long noncoding RNA XIST has been found involved in the development of DKD. A total of 1184 hospitalized patients with diabetes were included and divided into four groups based on their estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (UACR): normal control group (nDKD), DKD with normoalbuminuric and reduced eGFR (NA-DKD), DKD with albuminuria but without reduced eGFR (A-DKD), and DKD with albuminuria and reduced eGFR (Mixed), and then their clinical characteristics were analyzed. Peripheral blood mononuclear cells (PBMCs) of patients with DKD were isolated, and lncRNA XIST expression was detected by real-time quantitative PCR. The prevalence of DKD in hospitalized patients with diabetes mellutus (DM) was 39.9%, and the prevalence of albuminuria and decreased eGFR was 36.6% and 16.2%, respectively. NA-DKD, A-DKD, and Mixed groups accounted for 23.7%, 3.3%, and 12.9%, respectively. Women with DKD had considerably lower levels of lncRNA XIST expression in their PBMCs compared to nDKD. There was a significant correlation between eGFR level and lncRNA XIST expression (R = 0.390, P = 0.036) as well as a negative correlation between HbA1c and lncRNA XIST expression (R = -0.425, P = 0.027) in female patients with DKD. Our study revealed that 39.9% of DM inpatients who were admitted to the hospital had DKD. Importantly, lncRNA XIST expression in PBMCs of female patients with DKD was significantly correlated with eGFR and HbA1c.

Naringenin induces the cell apoptosis of acute myeloid leukemia cells by regulating the lncRNA XIST/miR-34a/HDAC1 signaling

Acute myeloid leukemia (AML) is a life-threatening aggressive malignancy of the bone marrow and has posed a great challenge to the clinic, due to a lack of fully understanding of the molecular mechanism. Histone deacetylase 1 (HDAC1) has been reported to be a therapeutic target for treating AML. Naringenin (Nar) may act as an anti-leukemic agent and suppress the expression of HDACs. However, the potential underlying mechanism of Nar in suppressing the activity of HDAC1 remains unclear. Here, we found that Nar induced the apoptosis, decreased the expression of lncRNA XIST and HDAC1, and increased the expression of microRNA-34a in HL60 cells. Sh-XIST transfection could induce cell apoptosis. On the contrary, the forced expression of XIST might reverse the biological actions of Nar. XIST could sponge miR-34a, which targeted to degrade HDAC1. The forced expression of HDAC1 could effectively reverse the effects of Nar. Thus, Nar can induce cell apoptosis by mediating the expression of lncRNA XIST/miR-34a/HDAC1 signaling in HL60 cells.

IncRNA XIST Stimulates Papillary Thyroid Cancer Development through the miR-330-3p/PDE5A Axis

Long non-coding RNAs (lncRNAs) possess both tumor suppressive and oncogenic functions in papillary thyroid cancer (PTC). Among all the thyroid cancers, PTC is the most prevalent form. Herein, we aim to determine the regulatory mechanisms and functions of lncRNA XIST in the multiplication, invasion, and survival of PTC. Quantitative reverse transcription polymerase chain reaction and Western blot experiments were performed to determine the patterns of lncRNA XIST, miR-330-3p, and PDE5A expressions. The subcellular localization of XIST was determined through subcellular fractionation. Bioinformatics analyses were performed to determine miR-330-3p's relationships with XIST and PDE5A, which were further confirmed through luciferase reporter assays. Loss-of-function combined with Transwell, CCK-8, and caspase-3 activity experiments were performed to determine the mechanism of the XIST/miR-330-3p/PDE5A axis in regulating the malignancy of PTC cells. Xenograft tumor experiment was employed to study the influence of XIST on tumor development in vivo. The PTC cell lines and tissues manifested considerably high levels of lncRNA XIST expression. The XIST knockdown inhibited proliferation, blocked migration, and strengthened apoptosis among PTC cells. Moreover, its knockdown suppressed PTC tumor development in vivo. XIST repressed miR-330-3p to stimulate the malignant behaviors of PTC. Through the downregulation of PDE5A, miR-330-3p attenuated the capability of PTC cells to grow, migrate, and survive. lncRNA XIST promotes tumor development in PTC through the regulation of the miR-330-3p/PDE5A axis. The findings from this study provide new insights into the treatment of PTC.

Integrated Bioinformatics and Validation of lncRNA-Mediated ceRNA Network in Myocardial Ischemia/Reperfusion Injury.

Background Myocardial ischemia/reperfusion (MI/R) injury is a common pathology in ischemia heart disease. Long noncoding RNAs (lncRNAs) are significant regulators related to many ischemia/reperfusion conditions. This study is aimed at exploring the molecule mechanism of lncRNA-mediated competing endogenous RNA (ceRNA) network in MI/R. Methods The dataset profiles of MI/R and normal tissues (GSE130217 and GSE124176) were obtained from the GEO database. Integrated bioinformatics were performed to screen out differentially expressed genes (DEGs). Thereafter, an lncRNA-mediated ceRNA network was constructed by the starBase database. The GO annotations and KEGG pathway analysis were conducted to study action mechanism and related pathways of DEGs in MI/R. A model of hypoxia/reoxygenation- (H/R-) treated HL-1 cell was performed to verify the expression of lncRNAs through qRT-PCR. Results 2406 differentially expressed- (DE-) mRNAs, 70 DE-lncRNAs, and 156 DE-miRNAs were acquired. These DEGs were conducted to construct an lncRNA-mediated ceRNA network, and a subnetwork including lncRNA Xist/miRNA-133c/mRNA (Slc30a9) was screen out. The functional enrichment analyses revealed that the lncRNAs involved in the ceRNA network might functions in oxidative stress and calcium signaling pathway. The lncRNA Xist expression is reduced under H/R conditions, followed by the increased level of miRNA-133c, thus downregulating the expression of Slc30a9. Conclusion In sum, the identified ceRNA network which included the lncRNA Xist/miR-133c/Slc30a9 axis might contribute a better understanding to the pathogenesis and development of MI/R injury and offer a novel targeted therapy way.

Sinomenine Suppressed Keratinocyte Proliferation and Imiquimod-Induced Psoriasis-Like Dermatitis by Regulating lncRNA XIST

Background: Psoriasis is a chronic inflammatory skin disease. Sinomenine (SIN) has anti-inflammatory and antioxidant effects. Objective: The objective of this study was to confirm the anti-inflammatory effects and mechanism of SIN in imiquimod (IMQ)-induced psoriasis-like mouse model and IMQ-induced differentiated human keratinocytes (HaCaT) cells. Methods: BALB/c mice were treated with IMQ to construct a psoriasis-like mice model. PASI score and HE staining were used to observe pathology injury of skin tissue. The secretion of inflammatory factors and the oxidative stress level were detected by ELISA. HaCaT cells after induction of differentiation were treated with IMQ (100 μM) and SIN (10 μg/mL or 50 μg/mL), cell viability, the secretion of inflammatory factors, and the oxidative stress level were detected by MTT assay, ELISA, respectively. The expression of lncRNA XIST was detected by RT-qPCR. The relationship between XIST and EIF4G2 protein was detected by RNA immunoprecipitation (RIP) assay and ubiquitination experiment. Results: SIN significantly reduced PASI score, epidermal thickness, inflammatory response, and oxidative stress levels that increased by IMQ in vivo. SIN inhibited IMQ-induced HaCaT cell proliferation, inflammatory response, and oxidative stress levels and decreased the expression of XIST. Overexpression of XIST negated the protective effect of SIN on HaCaT cells. XIST interacted directly with EIF4G2 and regulated EIF4G2 expression via K48 ubiquitin. Knockdown of XIST reduced the half-life of EIF4G2 and decreased EIF4G2 protein stability. In addition, the E3 ubiquitin protein ligase MDM2 interacted with EIF4G2 and downregulated EIF4G2 expression. XIST reduced the interaction between MDM2 and EIF4G2, which mediated EIF4G2 K48 ubiquitination. Overexpression of XIST negated the protective effect of SIN on the inflammation of HaCaT cells through activating the NF-κB signaling pathway, while NF-κB pathway inhibitor PDTC reversed this result. Conclusion: SIN had a protective effect on psoriasis and could inhibit HaCaT cell proliferation and inflammatory response via XIST/MDM2/EIF4G2/NF-κB axis.

LncRNA XIST is associated with preeclampsia and mediates trophoblast cell invasion via miR-340-5p/KCNJ16 signaling pathway

BackgroundPreeclampsia (PE) is a syndrome commonly occurring among the pregnant. Shallow trophoblast invasion is considered to be closely related to PE. Therefore, in trophoblast cells, we explored the potential mechanisms of lncRNA XIST in the modulation of trophoblast invasion and proliferation. MethodsGEO online analyzer was used to screen the abnormally expressed RNAs in placenta tissues from patients with severe PE and healthy controls. The prediction of target bindings was performed on TargetScan and starBase. Transfection was conducted to regulate the RNA expression levels in trophoblast cells, HTR-8/SVneo. RT-qPCR measured expression of lncRNA XIST, miR-340-5p and KCNJ16. The CCK-8 assay examined cell viability. Flow cytometer analyzed apoptosis and luciferase assay determined the luciferase activity. Transwell assays detected the invasion and western blot verified the changes in protein expression of MMP2, MMP9 and KCNJ16 in trophoblast cells. ResultslncRNA XIST expression was enhanced in PE patients. Upregulation of lncRNA XIST in HTR-8/SVneo cells inhibited the cell proliferation and invasion, and induced apoptosis. XIST upregulation inhibited MMP2 and MMP9 protein expression. lncRNA XIST/ KCNJ16 interplayed as ceRNAs of miR-340-5p. Specifically,miR-340-5p overexpression reversed the effect of XIST upregulation on the cell apoptosis, proliferation and invasive ability and the knockdown of KCNJ16 could add to the effect of miR-340-5p overexpression in HTR-8/SVneo. ConclusionlncRNA XIST was upregulated in PE. Upregulation of lncRNA XIST exerted the inhibitory effects on the proliferation and invasion of trophoblast cells through the interactions with miR-340-5p/KCNJ16, which suggests that the lncRNA XIST/miR-340-5p/KCNJ16 axis might play a role in PE.

Long Non-Coding RNA X-Inactive Specific Transcript (LncRNA Xist) Improves the Repair of Nerve Function in Spinal Cord Injury Models via Targeting CXC Motif Chemokine Receptor 4 (CXCR4) in Bone Mesenchymal Stem Cells (BMSCs)

This study assessed the effect of lncRNA Xist on the repair of neural function in spinal cord injury (SCI) model. Rat SCI model was established and assigned into blank group, Mock siRNA group and Xist siRNA group followed by analysis of the differentiation of BMSCs and rats’ neural functional recovery. The volume of mineralized nodule and quantity of LD in Xist siRNA group was significantly higher than control group and Mock siRNA group (P &lt; 0.05). The expression of RUNX2, ALP, OCN, lncRNA Xist, and CXCR4 in Xist siRNA group was also significantly increased compared to other two groups (P &lt; 0.05) along with elevated cell proliferation rate in Xist siRNA group. However, no differences of above parameters were found between control group and Mock siRNA group (P &gt; 0.05). In conclusion, lncRNA Xist promotes the repair of rats’ neurological function and the adilpogenesis and osteogenesis differentiation of BMSCs via targeting CXCR4 in SCI model, indicating that it might be a novel target for treating SCI.

A novel lncRNA-miRNA-mRNA triple network identifies lncRNA XIST as a biomarker for acute myocardial infarction.

Despite the well-established role of long non-coding RNAs (lncRNAs) across various biological processes, their mechanisms in acute myocardial infarction (AMI) are not fully elucidated. The GSE34198 dataset from the Gene Expression Omnibus (GEO) database, which comprised 49 specimens from individuals with AMI and 47 specimens from controls, was extracted and analysed using the weighted gene co-expression network analysis (WGCNA) package. Twenty-seven key genes were identified through a combination of the degree and gene significance (GS) values, and the CDC42 (degree = 64), JAK2 (degree = 41), and CHUK (degree = 30) genes were identified as having the top three-degree values among the 27 genes. Potential interactions between lncRNA, miRNAs and mRNAs were predicted using the starBase V3.0 database, and a lncRNA-miRNA-mRNA triple network containing the lncRNA XIST, twenty-one miRNAs and three hub genes (CDC42, JAK2 and CHUK) was identified. RT–qPCR validation showed that the expression of the JAK2 and CDC42 genes and the lncRNA XIST was noticeably increased in samples from patients with AMI compared to normal samples. Pearson’s correlation analysis also proved that JAK2 and CDC42 expression levels correlated positively with lncRNA XIST expression levels. The area under ROC curve (AUC) of lncRNA XIST was 0.886, and the diagnostic efficacy of the lncRNA XIST was significantly better than that of JAK2 and CDC42. The results suggested that the lncRNA XIST appears to be a risk factor for AMI likely through its ability to regulate JAK2 and CDC42 gene expressions, and it is expected to be a novel and reliable biomarker for the diagnosis of AMI.

Effect of LncRNA XIST on Immune Cells of Primary Biliary Cholangitis.

ObjectivePrimary biliary cholangitis (PBC) is an autoimmune disease with significant gender difference. X chromosome inactivation (XCI) plays important roles in susceptibility to diseases between genders. This work focuses on the differences of LncRNA XIST in several defined immune cells populations as well as its effects on naive CD4+ T cells proliferation and differentiation in patients with PBC.MethodsNKs, B cells, CD4+ T, and CD8+ T cells were separated by MicroBeads from peripheral blood mononuclear cells (PBMCs) of PBC patients and healthy control (HC). The expression levels of LncRNA XIST in these immune cells were quantified by qRT-PCR and their subcellular localized analyzed by FISH. Lentivirus were used to interfere the expression of LncRNA XIST, and CCK8 was used to detect the proliferation of naive CD4+ T cells in PBC patients. Finally, naive CD4+ T cells were co-cultured with the bile duct epithelial cells (BECs), and the effects of LncRNA XIST on the typing of naive CD4+ T cells and related cytokines were determined by qRT-PCR and ELISA.ResultsThe expression levels of LncRNA XIST in NKs and CD4+ T cells in PBC patients were significantly higher than those in HC, and were primarily located at the nucleus. LncRNA XIST could promote the proliferation of naive CD4+ T cells. When naive CD4+ T cells were co-cultured with BECs, the expressions of IFN-γ, IL-17, T-bet and RORγt in naive CD4+ T cells were decreased.ConclusionLncRNA XIST was associated with lymphocyte abnormalities in patients with PBC. The high expression of LncRNA XIST could stimulate proliferation and differentiation of naive CD4+ T cells, which might account for the high occurrence of PBC in female.