miR-181a mediates metabolic shift in colon cancer cells via the PTEN/AKT pathway

Cancer cell metabolism is often characterized by a shift from an oxidative to a glycolytic bioenergetics pathway, a phenomenon known as the warburg effect. Whether the deregulation of miRNAs contributes to the warburg effect remains largely unknown. Here we show that miR-181a expression is increased and thus induces a metabolic shift in colon cancer cells. miR-181a performs this function by inhibiting the expression of PTEN, leading to an increase of phosphorylated AKT which triggers metabolic shift. The increase of lactate production induced by miR-181a results in the rapid growth of cancer cells. These results identify miR-181a as a molecular switch involved in the orchestration of the warburg effect in colon cancer cells via the PTEN/AKT pathway.     

Serum protein oxidation and apolipoprotein CIII levels in people with systemic lupus erythematosus with and without nephritis

Increased oxidative stress is a hallmark of the autoimmune disease systemic lupus erythematosus (SLE). This study compares serum protein oxidation levels in SLE patients without and with renal involvement (lupus nephritis); the latter have a significantly poorer prognosis. Similar increases in protein carbonyls and decreases in protein thiols were observed in both SLE groups compared to controls. Protein carbonyl distribution, determined by Western blotting of 2D gels, was similar in both SLE groups, suggesting factors other than oxidation also play a role in SLE complications. 2D electrophoresis examined the serum proteome further. Six proteins were significantly decreased in non-renal SLE patients compared to controls; five were identified by mass spectrometry, including one isoform of pro-atherogenic apoCIII. Total apoCIII levels (assessed by ELISA) in lupus nephritis patients were significantly elevated compared to controls or non-renal SLE patients. Thus, levels of oxidized proteins and apoCIII may be useful biomarkers in SLE studies.     

LncRNA CCAT1 modulates the sensitivity of paclitaxel in nasopharynx cancers cells via miR-181a/CPEB2 axis

Recent studies reported that long non-coding RNA (lncRNA) might play critical roles in regulating chemo-resistant of multiple types of cancer. This study aimed to investigate whether long non-coding RNA CCAT1 was involved in Paclitaxel resistance in nasopharyngeal carcinoma (NPC). qRT-PCR was used for testing the expression of CCAT1, miR-181a and CPEB2 in tumor tissues and NPC cancers. NPC cells were transfected with siRNAs to suppress the mRNA level of CCAT1 in NPC cells. MTT assays and flow cytometry analysis were used to assess the sensitivity of paclitaxel in NPC cells. Luciferase reporter assays were used to examine the interaction of CCAT1 or CPEB2 to miR-181a. Our findings revealed that the upregulated CCAT1 results in significantly enhancing paclitaxel resistance in nasopharyngeal cancer cells. Bioinformatics analysis and luciferase reporter assay indicated that the upregulated CCAT1 sponges miR-181a in NPC cells. Furthermore, RNA immuno-precipitation assays showed that miR-181a could directly bind to CCAT1 mRNA in NPC cells. We restored miR-181a in NPC cells, and found restoration of miR-181a re-sensitized the NPC cells to paclitaxel in vitro. In addition, our results also showed that miR-181a was a modulator of paclitaxel sensitivity due to its regulative effect on cell apoptosis via targeting CPEB2 in NPC cells. Taken together, lncRNA CCAT1 regulates the sensitivity of paclitaxel in NPC cells via miR-181a/CPEB2 axis.     

miR-181a Modulation of ERK-MAPK Signaling Sustains DC-SIGN Expression and Limits Activation of Monocyte-Derived Dendritic Cells

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Serum miR-146a and miR-223 as potential new biomarkers for sepsis

Objective

Current biomarkers cannot completely distinguish sepsis from systemic inflammatory response syndrome (SIRS) caused by other non-infectious diseases. Circulating microRNAs (miRNAs) are promising biomarkers for several diseases, but their correlation with sepsis is not totally clarified.

Methods

Seven miRNAs related to inflammation or infection were included in the present study. Serum miRNA expression was investigated in 50 patients diagnosed with sepsis, 30 patients with SIRS and 20 healthy controls to evaluate the diagnostic and prognostic value. Expression levels of serum miRNAs were determined by quantitative PCR using the Qiagen miScript system. Serum CRP and IL-6 levels were determined by enzyme linked immunosorbent assay.

Results

Serum miR-146a and miR-223 were significantly reduced in septic patients compared with SIRS patients and healthy controls. The areas under the receiver operating characteristic curve of miR-146a, miR-223 and IL-6 were 0.858, 0.804 and 0.785, respectively.

Conclusion

Serum miR-146a and miR-223 might serve as new biomarkers for sepsis with high specificity and sensitivity. (ClinicalTrials.gov number, NCT00862290.)     

狼疮肾炎患者外周血单个核细胞钙调神经磷酸酶活性的检测及CD40L表达变化

目的:检测活动性狼疮肾炎(LN)患者外周血单个核细胞(PBMC)钙调神经磷酸酶(calcineurin,CaN)活性及其与PBMC CD40L表达的关系.方法:体外培养活动性LN患者PBMC,应用发色底物法检测胞浆CaN活性,流式细胞仪检测细胞CD40L的表达.结果:①在单纯培养情况下,正常对照组和LN组PBMC均出现一定量CaN活化,活动性LN组显著高于正常对照组(46.08±5.58 nrmmol/mg pro vs 8.81±3.61nmol/mg pro,P＜0.01);在PMA Ionomycin刺激下,各组CaN活性均升高,活动性LN组CaN活性明显高于正常对照组(69.34±12.59 nmol/mg provs 37.12±11.57 hmol/mg pro,P＜0.01);②LN患者PBMC在单纯培养和PMA Ionomycin刺激时CD40L蛋白和mRNA表达均显著高于相应的对照组(P＜0.01);③在单纯培养和PMA Ionomycin刺激时,FK506对LNPBMC表达CD40L蛋白和mRNA均有显著抑制作用(P＜0.01).结论:LN患者PBMC存在CaN过度活化;LN患者PBMC高效表达CD40L与其CaN过度活化密切相关,通过阻断CaN活化可调控CD40-CD40L共刺激信号途径的活化.     

Circulating miR-3613-5p but not miR-125b-5p,miR-199a-3p,and miR-451a are biomarkers of endometriosis

ObjectiveThis study aimed to assess the utility of circulating miR-125b-5p, miR-199a-3p, miR-451a, and miR-3613-5p as biomarkers of endometriosis.Study designPatients with stage III or IV of endometriosis according to the revised American Society of Reproductive Medicine (rASRM) staging classification, as well as control women, were recruited. We created a prospective study conducted on a group of 48 patients (n = 25 controls, n = 24 endometriosis) who had laparoscopic surgery. Blood samples were taken and plasma miRNA levels were measured by quantitative real-time polymerase chain reaction (RT-qPCR) and assessed with AUC and ROC curves.ResultsMiR-451a and miR-3613-5p were significantly decreased in the plasma of endometriosis patients. miR-451a had a receiver-operating characteristic (ROC) area under the curve 0.8283 and miR-3613-5p had a ROC area under the curve 0.7617. The concentration of circulating miR-125b-5p and miR-199-3p did not differ between endometriosis patients and controls. Plasma miRNA levels did not change with BMI, smoking status, fertility problems, or menstrual pain according to the VAS scale (p > 0.05).ConclusionCirculating miR-451a and miR-3613-5p levels significantly differed between endometriosis and controls. However, the levels of miR-451a were discordant with previous studies. Therefore, miR-3613-5p may have better potential as the endometriosis biomarker. Circulating miR-125b-5p and miR-199a-3p cannot be used as reliable markers of endometriosis.     

外周血miR-223和血清BNP水平在慢性心力衰竭患者中的诊断价值

目的:探究慢性心力衰竭(chronic heart failure,CHF)患者外周血microRNA-223(miR-223)和血清B型利钠肽(B-type natriuretic peptide,BNP)水平及其诊断价值。方法:选取CHF患者65例(CHF组),其中美国纽约心脏病协会(New York Heart Association,NYHA)心功能分级Ⅱ级24例,Ⅲ级22例,Ⅳ级19例。另取40例同期在体检中心进行健康体检者(Control组),采用实时荧光定量PCR检测外周血中miR-223水平,ELISA检测血清BNP含量,ROC曲线评价miR-223及BNP对CHF的诊断价值。结果:CHF组左心室短轴缩短率及左心室射血分数显著低于Control组(P0.01);左心室舒张末期内径显著高于Control组(P0.01)。CHF组不同NYHA心功能分级患者miR-223和BNP水平均高于Control组,且miR-223和BNP水平随NYHA心功能分级逐渐递增,组间两两比较均显示统计学差异(P0.05)。miR-223诊断CHF的曲线下面积(area under the curve,AUC)为0.7375,临界值为43.51时灵敏度为92.82%,特异度为89.44%;BNP诊断CHF的AUC为0.7925,临界值为128 ng/L时灵敏度为92.93%,特异度为92.58%。结论:CHF患者外周血miR-223和血清BNP水平高于健康对照人群,其对CHF的诊断具有一定的临床参考价值。     

Dysregulated expression of STAT1, miR-150, and miR-223 in peripheral blood mononuclear cells of coronary artery disease patients with significant or insignificant stenosis

Coronary artery disease (CAD) is a multicellular disease characterized by chronic inflammation. Peripheral blood-mononuclear cells (PBMCs), as a critical component of immune system, actively cross-talk with pathophysiological conditions induced by endothelial cell injury, reflecting in perturbed PBMC expression. STAT1 is believed to be relevant to CAD pathogenesis through regulating key inflammatory processes and modulating STAT1 expression play key roles in fine-tuning CAD-related inflammatory processes. This study evaluated PBMC expressions of STAT1, and its regulators (miR-150 and miR-223) in a cohort including 72 patients with CAD with significant ( ≥ 50%) stenosis, 30 patients with insignificant ( < 50%) coronary stenosis (ICAD), and 74 healthy controls, and assessed potential of PBMC expressions to discriminate between patients and controls. We designed quantitative real-time polymerase chain reaction (RT-qPCR) assays and identified stable reference genes for normalizing PBMC quantities of miR-150, miR-223, and STAT1 applying geNorm algorithm to six small RNAs and five mRNAs. There was no significant difference between CAD and ICAD patients regarding STAT1 expression. However, both groups of patients had higher levels of STAT1 than healthy controls. miR-150 and miR-223 were differently expressed across three groups of subjects and were downregulated in patients compared with healthy controls, with the lowest expression levels being observed in patients with ICAD. ROC curves suggested that PBMC expressions may separate between different groups of study subjects. PBMC expressions also discriminated different clinical manifestations of CAD from ICADs or healthy controls. In conclusion, the present study reported PBMC dysregulations of STAT1, miR-150, and miR-223, in patients with significant or insignificant coronary stenosis and suggested that these changes may have diagnostic implications.     

miRNA-155 and miRNA-181a as prognostic biomarkers for pediatric acute lymphoblastic leukemia

Mortality rates of acute lymphoblastic leukemia (ALL) have improved over the past 20 years; however, a significant portion of deaths stems from the lack of prognostic biomarkers, which can direct therapy and overcome drug resistance. microRNA-155a (miRNA-155a) and miRNA-181a are two single-stranded miRNAs involved in the pathogenesis of many types of leukemia and lymphoma and is linked to drug resistance. We investigated their expression levels in 55 patients, 45 diagnosed with ALL and 10 as a control group. We found that miRNA-155a and miRNA-181a were significantly upregulated in the ALL group with both being linked to high levels of minimal residual disease and poor prognosis. miRNA-155a cutoff value was significant in discriminating between high- and low-risk ALL patients as well as between ALL patients and healthy controls, miRNA-181a cutoff value, however, was not significant. Both markers levels were significantly downregulated after therapy. We conclude that miR-155 is correlated with poor prognosis in ALL, whereas we couldn’t link miRNA-181a to the prognosis in ALL. Moreover, the marked decrease in their expression after therapy could reflect their impact on disease outcome.     

Circular RNA hsa_circ_0076248 promotes oncogenesis of glioma by sponging miR-181a to modulate SIRT1 expression

Glioma is one of the most common primary malignancies of the central nervous system, which has aggressive clinical behavior and a poorer prognosis. MicroRNAs (miRs) are a class of small noncoding RNAs that function as mediators of gene expression, which can be sponged by circRNA provided with a closed circular structure. Dysregulations of circular RNAs (circRNAs) and miRs have been implicated in the development and progression of glioma. In the current study, we investigated the role of circular RNA hsa_circ_0076248 in mediating the oncogenesis of glioma by sponging miR-181a to modulate silent information regulator 1 (SIRT1) expression in vitro and in vivo. The quantitative real-time polymerase chain reaction results showed that the expression of miR-181a was significantly decreased in glioma tissues and cell lines compared with normal brain tissues and normal gliocyte, respectively, and the expression of hsa_circ_0076248 and SIRT1 demonstrated the opposite. Bioinformatics analysis identified hsa_circ_0076248 could sponge miR-181a, and miR-181a could target the mRNA of SIRT1. Our results verified that downregulating hsa_circ_0076248 or upregulating miR-181a could depress the proliferation and invasion of glioma in vitro and in vivo. The experiment also showed that downregulating hsa_circ_0076248 or upregulating miR-181a could remarkably promote the temozolomide chemotherapy sensitivity. Furthermore, Western blot analysis testified that downregulating hsa_circ_0076248 or upregulating miR-181a could promote the expression of p53 and SIRT1. In summary, our study sheds light on the regulatory mechanism of hsa_circ_0076248 in glioma growth and invasion via sponging miR-181a, which downregulates the SIRT1 expression and also suggests that hsa_circ_0076248, miR-181a, and SIRT1 may serve as potential therapeutic targets for glioma.     

Genotypic analysis of the TGF beta-509 allele in patients with systemic lupus erythematosus and Sjögren's syndrome

Transforming growth factor beta (TGFβ) is a secreted protein present in the circulation and is a critical regulator of the body's immune system. TGFβ is believed to control several components of the immune system and inhibit autoimmune reactions. Systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) are prototypical human autoimmune diseases characterized by the circulating autoantibodies directed against nuclear antigens and immune complex deposition in various tissues leading to target organ inflammation and damage. Although the etiology of SLE is unknown, it has been observed that patients with SLE have lower levels of circulating TGFβ than healthy individuals. In addition, mice lacking the TGFβ1 gene develop a severe autoimmune disease that has features of both SS and SLE. Polymorphisms in the TGFβ1 gene may alter the mRNA expression levels and influence the plasma protein concentration. Of the known TGFβ 1 polymorphisms, only the C-509T polymorphism in the promoter region has been shown to be significantly associated with the plasma concentrations of TGFβ 1. In this study, we have conducted a blinded study to determine if the -509 TGFβ1 gene polymorphism is associated with SS or SLE. Genomic PCR and RFLP analysis of a 441 bp sequence encompassing the -509 polymorphism of the TGFβ gene indicated that there were no statistically significant clinical correlations.     

Elevation of human tumor necrosis factor-like weak inducer of apoptosis in peripheral blood mononuclear cells is correlated with disease activity and lupus nephritis in patients with systemic lupus erythematosus

Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a recently identified proinflammatory cytokine of the TNF superfamily. Studies have indicated that TWEAK plays an important role in renal, vascular injury and immune disease. The aim of this study was to explore the expression of the TWEAK in peripheral blood mononuclear cells (PBMCs) and analyze the correlation between TWEAK and disease activity and renal damage of SLE. The expression of TWEAK in PBMCs was determined by RT-PCR and western blot. SLE disease activity was evaluated by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2000 score. Next were analyzed the correlations of TWEAK mRNA and protein to serum IL-10, MCP-1 and some laboratory parameters of SLE disease activity. Subjects comprised 48 patients with SLE including 25 patients with renal damage and 23 without, 20 patients with rheumatoid arthrithis (RA) and 15 healthy controls. The results showed that TWEAK expressions in PBMCs from SLE patients were significantly higher than that in RA patients or healthy controls, especially higher in those patients with renal disease. Elevated production of TWEAK is correlated positively and significantly with SLEDAI, proteinuria, serum anti-dsDNA, IL-10 and MCP-1, but inversely associated with serum complements. Our results suggested that TWEAK in PBMCs is positively related to SLE disease activity and might be involved in the pathogenesis of SLE.     

Suppression of miR-181a attenuates H2O2-induced death of mesenchymal stem cells by maintaining hexokinase II expression

Background

Low survival rate of transplanted cells compromises the efficacy of cell therapy. Hexokinase II (HKII) is known to have anti-apoptotic activity through its interaction with mitochondria. The objective was to identify miRNAs targeting HKII and investigate whether miRNA-mediated modulation of HKII could improve the survival of mesenchymal stem cells (MSCs) exposed to H₂O₂. The expression of HKII in MSCs exposed to H₂O₂ was evaluated, and HKII-targeting miRNA was screened based on miRNA-target prediction databases. The effect of H₂O₂ on the expression of the selected HKII-targeting miRNA was examined and the effect of modulation of the selected HKII-targeting miRNA using anti-miRNA on H₂O₂-induced apoptosis of MSC was evaluated.

Results

H₂O₂ (600 μM) induced cell death of MSCs and decreased mitochondrial HKII expression. We have identified miR-181a as a HKII-targeting miRNA and H₂O₂ increased the expression of miR-181a in MSCs. Delivery of anti-miR-181a, which neutralizes endogenous miR-181a, significantly attenuated H₂O₂-induced decrease of HKII expression and disruption of mitochondrial membrane potential, improving the survival of MSCs exposed to H₂O₂.

Conclusions

These findings suggest that H₂O₂-induced up-regulation of miR-181a contributes to the cell death of MSCs by down-regulating HKII. Neutralizing miR-181a can be an effective way to prime MSCs for transplantation into ischemic tissues.     

miRNA-181a在胃癌细胞增殖和迁移中的作用

miRNA与恶性肿瘤患者的诊断和预后密切相关,为了考察miRNA-181a在胃癌细胞增殖和迁移中的作用,本研究检测了miRNA-181a在胃癌组织中的表达,并通过对人胃癌细胞系MGC-803转染miR-181a模拟物或抑制剂来考察miR-181a对细胞迁移和增殖的影响。RT-PCR显示,miRNA-181a在胃癌组织中的表达水平显著高于癌旁组织(p<0.05)。伤口愈合实验和Transwell实验显示,转染miR-181a抑制剂或TGF-β受体2(TGFβR2)过表达的pcDNA3.1质粒均可抑制MGC-803细胞的迁移。EdU实验和CCK-8实验显示,转染miR-181a抑制剂或TGFβR2过表达的pcDNA3.1质粒均可抑制MGC-803细胞的增殖。此外,miR-181a抑制剂处理可使TGFβR2蛋白表达明显升高。然而,miR-181a模拟物或抑制剂处理后TGFβR2mRNA水平没有显著变化。总之,本研究表明高表达的miR-181a通过在转录后抑制TGFβR2蛋白表达来促进胃癌细胞的迁移和增殖。miR-181a有望成为胃癌的潜在治疗靶点。     

MicroRNA-181a enhances the chemoresistance of human cervical squamous cell carcinoma to cisplatin by targeting PRKCD

MicroRNAs(miRNAs) are involved in regulating the response of cancer cells to various therapeutic interventions, but their involvement in the chemoresistance of human cervical squamous cell carcinoma is not fully understood. We found miR-181a was significantly up-regulated in specimens from patients with chemoresistant cervical squamous cell carcinoma. In this study, we aimed to clarify the role of miR-181a in regulating the chemoresistance of cervical cancer. Two human cervical squamous cancer cell lines, SiHa and Me180, were used. Enforced expression of miR-181a enhanced chemoresistance to cisplatin in cervical cancer cells through apoptosis reversion. In a nude mouse xenograft model, the overexpression of miR-181a markedly inhibited the therapeutic response to cisplatin. PRKCD, a target gene of miR-181a and a promoter of apoptosis, was negatively regulated by miR-181a. We found that the effect of miR-181a on chemoresistance was mediated by PRKCD. Additionally, silencing of PRKCD yielded an effect similar to that of miR-181a up-regulation and inhibited apoptosis in cervical cancer cells. Our findings suggest that miR-181a may function as an oncogene and induce chemoresistance in cervical squamous cell carcinoma cells at least in part by down-regulating PRKCD, thus may provide a biomarker for predicting chemosensitivity to cisplatin in patients with cervical squamous cancer.     

Knockdown of TRIM27 expression suppresses the dysfunction of mesangial cells in lupus nephritis by FoxO1 pathway

TRIM27 (tripartite motif-containing 27) is a member of the TRIM (tripartite motif) protein family and participates in a variety of biological processes. Some research has reported that TRIM27 was highly expressed in certain kinds of carcinoma cells and tissues and played an important role in the proliferation of carcinoma cells. However, whether TRIM27 takes part in the progression of lupus nephritis (LN) especially in cells proliferation remains unclear. Our study revealed that the overexpression of TRIM27 was observed in the kidneys of patients with LN, lupus mice and mesangial cells exposed to LN plasma which correlated with the proliferation of mesangial cells and ECM (extracellular matrix) deposition. Downregulation of TRIM27 expression suppressed the proliferation of mesangial cells and ECM accumulation in MRL/lpr mice and cultured human mesangial cells (HMCs) by regulating the FoxO1 pathway. Furthermore, the overexpression of FoxO1 remarkably decreased HMCs proliferation level and ECM accumulation in LN plasma-treated HMCs. In addition, the protein kinase B (Akt) signal pathway inhibitor LY294002 significantly reduced the expression of TRIM27 and inhibited the dysfunction of mesangial cells. These above data suggested that TRIM27 mediated abnormal mesangial cell proliferation in kidney of lupus and might be the potential target for treating mesangial cell proliferation of lupus nephritis.     

Association of LncRNA-GAS5 gene polymorphisms and PBMC LncRNA-GAS5 level with risk of systemic lupus erythematosus in Chinese population

Growth arrest-specific 5 (GAS5) is a kind of long non-coding RNAs (lncRNAs). Previous studies showed that down-regulation of LncRNA-GAS5 was involved in the development of systemic lupus erythematosus (SLE). However, the regulatory mechanism of down-expressed LncRNA-GAS5 in SLE remains obscure. In this study, we aimed to investigate the association of LncRNA-GAS5 polymorphism with SLE risk. And further explore how LncRNA-GAS5 is involved in the occurrence of SLE. Here, we evaluated the relationship between the risk for the development of SLE and the 5-base pair (AGGCA/-) insertion/deletion (I/D) polymorphism (rs145204276) in the LncRNA-GAS5 promoter region. A custom 36-Plex SNPscan kit was used for genotyping the LncRNA-GAS5 polymorphisms. The LncRNA-GAS5 and miR-21 target prediction was performed using bioinformatics software. Enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR (qRT-PCR) were performed to assess GAS5 and miR-21 mRNA expression and PTEN protein expression. The results revealed that rs145204276 resulted in a decreased risk of SLE (DD genotypes vs II genotypes: adjusted OR = 0.538, 95% CI, 0.30-0.97, P = .039; ID genotypes vs II genotypes: adjusted OR = 0.641, 95% CI, 0.46-0.89, P = .007; ID/DD genotypes vs II genotypes: adjusted OR = 0.621, 95% CI, 0.46-0.84, P = .002; D alleles vs I alleles: adjusted OR = 0.680, 95% CI, 0.53-0.87, P = .002). A reduced incidence of renal disorders in SLE was found to be related to ID/DD genotypes and D alleles (ID/DD genotypes vs II genotypes: OR = 0.57, 95% CI, 0.36-0.92, P = .020; D alleles vs I alleles: OR = 0.63, 95% CI, 0.43-0.93, P = .019). However, no significant association of rs2235095, rs6790, rs2067079 and rs1951625 polymorphisms with SLE risk was observed (P > .05). Additionally, haplotype analysis showed that a decreased SLE risk resulted from the A-A-C-G-D haplotype (OR = 0.67, 95% CI, 0.49-0.91, P = .010). Also, patients in the SLE group showed a down-regulated expression of LncRNA-GAS5 and PTEN than the healthy volunteers; however, patients with rs145204276 ID/DD genotypes showed up-regulated expression of LncRNA-GAS5 and PTEN compared with patients carrying the II genotype. Furthermore, the miR-21 levels were considerably up-regulated in the SLE group than the healthy volunteers, and patients with rs145204276 ID/DD genotype had lower miR-21 levels than the ones with the II genotype. Thus, we found that the LncRNA-GAS5/miR-21/PTEN signalling pathway was involved in the development of SLE, where LncRNA-GAS5 acted as an miR-21 target, and miR-21 regulated the expression of PTEN. These findings indicated that the rs145204276 ID/DD genotypes in the LncRNA-GAS5 gene promoter region may be protected against SLE by up-regulating the expression of LncRNA-GAS5, which consecutively regulated miR-21 and PTEN levels.     

Atacicept in combination with MMF and corticosteroids in lupus nephritis: results of a prematurely terminated trial

Introduction  

Atacicept is a soluble, fully human, recombinant fusion protein that inhibits B cell-stimulating factors APRIL (a proliferation-inducing ligand) and BLyS (B-lymphocyte stimulator). The APRIL- LN study aimed to evaluate the efficacy and safety of atacicept in patients with active lupus nephritis (LN), receiving newly initiated corticosteroids (CS) and mycophenolate mofetil (MMF).