Potential Biomarker and Therapeutic LncRNAs in Multiple Sclerosis Through Targeting Memory B Cells

Ghoveud, Elahe; Teimuri, Shohreh; Vatandoost, Jafar; Hosseini, Aref; Ghaedi, Kamran; Etemadifar, Masoud; Nasr-Esfahani, Mohammad Hossein; Megraw, Timothy L.

doi:10.1007/s12017-019-08570-6

Cited by 23 publications

(13 citation statements)

References 45 publications

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“…Each circular node represents a protein encoded by a gene, the red nodes are the candidate mRNAs, and the line between nodes represents the interaction between proteins. Ghoveud et al, 2020). According to the GSEA in Figure 7, the expression of C3AR1 could affect the Wnt signaling pathway, and the expression of PAWR had an effect on the calcium signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that the C3a level in the plasma of patients with aneurysmal subarachnoid hemorrhage (aSAH) correlated significantly with bad outcome, and the C3a receptor antagonist (C3aRA) could improve the neurologic outcome of experimental ICH in mice ( Mack et al, 2007 ; Rynkowski et al, 2009 ). PAWR (pro-apoptotic WT1 regulator) is a pro-apoptotic gene that was among the top differentially expressed genes in peripheral blood mononuclear cells (PBMCs) from multiple sclerosis (MS) patients and might be involved in the regulation of MS ( Comabella et al, 2016 ; Ghoveud et al, 2020 ). According to the GSEA in Figure 7 , the expression of C3AR1 could affect the Wnt signaling pathway, and the expression of PAWR had an effect on the calcium signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

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Identification of Candidate Blood mRNA Biomarkers in Intracerebral Hemorrhage Using Integrated Microarray and Weighted Gene Co-expression Network Analysis

Jin

Hao

et al. 2021

Front. Genet.

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PurposeIntracerebral hemorrhage (ICH) is a serious public health hazard due to its high morbidity, disability, and mortality. Currently, the exact molecular mechanisms of ICH are unknown. We tried to identify the ICH-related candidate blood messenger RNA (mRNA) biomarkers by microarray analysis and weighted gene co-expression network analysis (WGCNA).Materials and MethodsWe collected the blood samples from patients with ICH (n = 4) and from vascular risk factor (VRF) controls (n = 4) and analyzed the mRNA expression profiles by competitive endogenous RNA (ceRNA) microarray. Differentially expressed genes (DEGs) were identified and then a weighted gene co-expression network was constructed. Modules with clinical significance were distinguished. Then, we downloaded two Gene Expression Omnibus (GEO) datasets (GSE24265 and GSE125512). Candidate mRNAs were identified by taking the intersection of the DEGs in our microarray, the interesting genes in the key module, and the DEGs in GSE24265. Functional analysis involving Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) and construction of a protein–protein interaction (PPI) network were conducted.ResultsA total of 340 DEGs in our microarray were identified between the ICH group and the control group. Among the eight gene modules established by WGCNA, the yellow module containing 191 genes was the most strongly associated with ICH. Four candidate mRNAs (C3AR1, PAWR, ARNTL2, and LDLRAD4) were identified. In the early stage of ICH (within 24 h), C3AR1, PAWR, and ARNTL2 were highly expressed in the perihematomal tissue, but with low expressions in peripheral blood; in the late stage (72 h after the first blood draw), an obvious upward trend of C3AR1 and PAWR in peripheral blood was seen. Functional analysis showed that candidate mRNAs were concerned with multiple pathways, such as the Wnt signaling pathway and calcium signaling pathway. They might affect the process of ICH through neuroinflammation, cell apoptosis, and pyroptosis.ConclusionWe identified four candidate blood mRNAs (C3AR1, PAWR, ARNTL2, and LDLRAD4) related to ICH. They showed different expression patterns in peripheral blood and perihematomal tissues and changed with time. They might play important roles in ICH through neuroinflammation, cell apoptosis, and pyroptosis and might shed new light to novel biomarkers or therapeutic targets in ICH.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Identification of Candidate Blood mRNA Biomarkers in Intracerebral Hemorrhage Using Integrated Microarray and Weighted Gene Co-expression Network Analysis

Jin

Hao

et al. 2021

Front. Genet.

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“…As sequencing technology has advanced, more non-coding RNA has been identified. Among these, lncRNAs have gotten a lot of interest because of their diverse roles in all stages of carcinogenesis and tumor development, and lncRNAs might be exploited as novel prognostic indicators ( 18 , 19 ). By influencing oncogenes or tumor suppressor genes, they contribute to tumor development, proliferation, and metastasis ( 20 , 21 ).…”

Section: Discussionmentioning

confidence: 99%

LncRNA SNHG7 Regulates Mesenchymal Stem Cell Through the Notch1/Jagged1/Hes-1 Signaling Pathway and Influences Folfirinox Resistance in Pancreatic Cancer

Cheng

Fan²,

Zhou

et al. 2021

Front. Oncol.

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Pancreatic cancer (PC) is one of the deadliest gastrointestinal cancers, accounting for the fourth highest number of cancer-related fatalities. Increasing data suggests that mesenchymal stem cells (MSCs) might influence the drug resistance of GC cells in the tumor microenvironment and play essential roles in drug resistance development. However, the precise underlying process remains a mystery. The purpose of this study was to look at the control of MSC-induced SNHG7 in pancreatic cancer. In vitro and in vivo sphere formation, colony formation, and flow cytometry investigations revealed the stemness and Folfirinox resistance in pancreatic cancer cells. To confirm the direct connections between SNHG7 and other related targets, RNA pulldown and immunoprecipitation tests were performed. MSC co-culture enhanced the stemness and Folfirinox resistance in pancreatic cancer cells according to the findings. MSC co-culture increased SNHG7 expression in pancreatic cancer cells, contributing to the stemness and Folfirinox resistance. We demonstrated that Notch1 interacted with SNHG7 and could reverse the facilitative effect of SNHG7 on the stemness and Folfirinox resistance in pancreatic cancer cells. Finally, our findings showed that MSCs increased SNHG7 expression in pancreatic cancer cells, promoting the stemness and Folfirinox resistance via the Notch1/Jagged1/Hes-1 signaling pathway. These findings could provide a novel approach and therapeutic target for pancreatic cancer patients.

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“…In CNS, they diversely participate in the neuroin ammation, synapse plasticity, synaptogenesis and memory formation [30,36,37]. Accumulating evidence has indicated that lncRNAs as key regulatory molecules are involved in MS pathogenesis [38][39][40][41][42], but these data mainly focused on the regulation of Th cells and microglia by lncRNAs. Given that astrocytes play essential roles in MS process, it is crucial to understand the mechanism exerted by astrocytes.…”

Section: Discussionmentioning

confidence: 99%

IL-9-triggered lncRNA Gm13568 regulates Notch1 in astrocytes through interaction with CBP/P300: contribute to the pathogenesis of experimental autoimmune encephalomyelitis

Liu

Zhou

Wang

et al. 2021

Preprint

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Background Interleukin 9 (IL-9), produced mainly by T helper 9 (Th9) cells, has been recognized as an important regulator in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Astrocytes respond to IL-9 and reactive astrocytes always associate with blood-brain barrier damage, immune cells infiltration and spinal injury in MS and EAE. Several long non-coding RNAs (lncRNAs) with aberrant expression have been identified in the pathogenesis of MS. Here, we examined the effects of lncRNA Gm13568 (a co-upregulated lncRNA both in EAE mice and in mouse primary astrocytes activated by IL-9) on the activation of astrocytes and the process of EAE. Methods In vitro, shRNA-recombinant lentivirus with Glial fibrillary acidic protein (GFAP) promoter were performed to determine the relative gene expression and proinflammatory cytokines production in IL-9 treated-astrocytes using Western blot, real-time PCR and Cytometric bead array, respectively. RIP and ChIP assays were analyzed for the mechanism of lncRNA Gm13568 regulating gene expression. Immunofluorescence assays was performed to measure the protein expression in astrocytes. In vivo, H&E staining and LFB staining were applied to detect the inflammatory cells infiltrations and the medullary sheath damage in spinal cords of EAE mice infected by the recombinant lentivirus. Results were analyzed by one-way ANOVA or student’s t-test, as appropriate. Results Knockdown of the endogenous lncRNA Gm13568 remarkably inhibits the Notch1 expression, astrocytosis and the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) as well as the production of inflammatory cytokines and chemokines (IL-6, TNF-α, IP-10) in IL-9 activated astrocytes. In which, Gm13568 associates with CBP/P300 is enriched in the promoter of Notch1 genes. More importantly, inhibiting Gm13568 with lentiviral vector in astrocytes ameliorates significantly inflammation and demyelination in EAE mice, therefore delaying the EAE process. Conclusions These findings uncover that Gm13568 regulates the production of inflammatory cytokines in active astrocytes and affects the pathogenesis of EAE through the Notch1/STAT3 pathway. LncRNA Gm13568 may be a promising target for treating MS and demyelinating diseases.

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Potential Biomarker and Therapeutic LncRNAs in Multiple Sclerosis Through Targeting Memory B Cells

Cited by 23 publications

References 45 publications

Identification of Candidate Blood mRNA Biomarkers in Intracerebral Hemorrhage Using Integrated Microarray and Weighted Gene Co-expression Network Analysis

Identification of Candidate Blood mRNA Biomarkers in Intracerebral Hemorrhage Using Integrated Microarray and Weighted Gene Co-expression Network Analysis

LncRNA SNHG7 Regulates Mesenchymal Stem Cell Through the Notch1/Jagged1/Hes-1 Signaling Pathway and Influences Folfirinox Resistance in Pancreatic Cancer

IL-9-triggered lncRNA Gm13568 regulates Notch1 in astrocytes through interaction with CBP/P300: contribute to the pathogenesis of experimental autoimmune encephalomyelitis

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