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Aberrant lncRNA and mRNA expression in patients with anti-N-methyl-D-aspartate receptor encephalitis

ABSTRACT: Background: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a nervous autoimmune disorder discovered in the recent more than fifteen years. To understand potential involvement of epigenetic mechanisms in pathogenesis of anti-NMDAR encephalitis, we initiated a study to compare the expression profiles of long non-coding RNAs (lncRNAs) and messenger RNA (mRNAs) in patients of anti-NMDAR encephalitis and healthy controls. Methods: 11 patients who were diagnosed with anti-NMDAR encephalitis were enrolled in our observational studies. Total RNA was extracted from patients’ plasma and the expression levels of lncRNAs and mRNAswere determined. Differential expression analysis via RNA sequencing, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, as well as a co-expression network of lncRNA-mRNA were performed in 5 patients and 5 healthy controls to evaluate potential the changes in expression patterns. The expression levels of certain lncRNAs and mRNAs were further validated in 11patients and 11 healthy controls using quantitative real-time polymerase chain reaction (qRT-PCR). Results: It was found that a total of 83 lncRNAs and 2345 mRNAs were differentially expressed in five patients with anti-NMDAR encephalitis compared with five healthy controls. Of those lncRNAs, 63 were upregulated and 20 downregulated, while 1509 mRNAs were upregulated and 836 downregulated. GO and KEGG pathway analyses showed that a wide range of biological functions were perturbed during acute anti-NMDAR encephalitis. Differentially expressed genes were found to be involved in autoimmune, B cell signaling, neuroinflammation, or synaptic plasticity. qRT-PCR was conducted in 11 patients and 11healthy controls to further confirm the levels of six lncRNAs and four mRNAs, and the results were found to be consistent with those by RNA sequencing. The co-expression networks of lncRNA-mRNA were performed in some meaningful KEGG analyses, including chemokine signaling pathway, Long-term potentiation, B cell receptor signaling pathway and MAPK signaling pathway. Conclusions: Taken together, these findings suggest the involvement of a number of molecular pathways in anti-NMDAR encephalitis, some of which could serve as potential biomarkers to assist in diagnosis, treatment and prognosis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE305025 | GEO | 2025/08/09

REPOSITORIES: GEO

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Project description:Background: The diagnosis and monitoring of Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis typically rely on clinical manifestations and the detecting of anti-NMDAR antibodies. However, several studies have found that anti-NMDAR IgG in serum is not entirely specific and can be detected in about 3% of healthy individuals. Objective: To identify novel biomarkers that can accurately monitor the severity of anti-NMDAR encephalitis. Methods: We enrolled 9 patients with anti-NMDAR encephalitis and categorized them into an acute-phase group and a stable-phase group based on the duration of illness and disease severity. The clinical severity of the patients was assessed using the modified Rankin Scale (mRS) and the clinical assessment scale for autoimmune encephalitis (CASE). Then, we isolated exosomal miRNAs from plasma samples and analysed the differentially expressed miRNAs through next-generation sequencing. The sequencing results were validated using RT-qPCR. Furthermore, we conducted correlation analyses between miRNAs and clinical severity. Finally, we performed the functional pathways analysis to explore the underlying mechanisms in anti-NMDAR encephalitis. Results: We have found that exosomal miR-432-5p, miR-4433b-5p and miR-599 exhibited significant differences between patients with anti-NMDAR encephalitis and healthy controls, as well as at different stages of the disease. The expressions of miR-432-5p and miR-4433b-5p were negatively correlated with both the mRS and the CASE. We further identified that the pathways involved in rhythmic processes and neuroinflammation, as well as glutamatergic signaling, play significant roles in the pathogenesis of anti-NMDAR encephalitis. Conclusions: Our research indicates that exosomal miR-432-5p, miR-4433b-5p and miR-599 were highly correlated with the severity of anti-NMDAR encephalitis and can serve as potential biomarkers for disease monitoring. We further identified the pathways play significant roles in anti-NMDAR encephalitis. By modulating the functions of these crucial pathways, we can potentially uncover novel therapeutic targets and improve patient outcomes.

Project description:Objective: The diagnostic roles of long non-coding RNAs (lncRNAs) in clear cell renal cell carcinoma (ccRCC) are still not well defined. We aimed to identify differentially expressed lncRNAs and mRNAs in plasma of ccRCC patients and health controls systematically. Methods: Expression profile of lncRNAs and mRNAs in plasma from ccRCC patients and healthy controls was analyzed by microarray assay. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway based approaches were used to investigate biological functions and signaling pathways affected by the differentially expressed mRNAs. SOCS2-AS1 was selected for validation using Real-Time PCR. The differentially expressed genes were further compared with E-MTAB-1830 datasets by Venn and NetworkAnalyst website. The expression level and overall survival (OS) of differentially expressed mRNAs were analyzed in GEPIA and ULCAN website. Results: Compared with healthy controls, a total of 3,664 differentially expressed lncRNAs were revealed by heatmap and volcano-plot, including up-regulation in 1,511 and down-regulation in 2,153 (fold change ≥ 2 and P < 0.05), respectively. And differential expression was noticed in 2,268 mRNAs, including up-regulation in 932 mRNAs and down-regulation in 1,336 mRNAs, respectively (fold change ≥ 2 and P < 0.05). Pathways analysis based on deregulated mRNAs were mainly involved in melanogenesis and Hippo signaling pathway (P < 0.05). The expression of SOCS2-AS1 was down in ccRCC plasma and tissues, as well as in cell lines, which was the same as the results of lncRNA microarray. Compared with the E-MTAB-1830 gene expression profiles, we identified 18 lncRNAs, and 87 mRNAs were differently expressed in both plasma and neoplastic tissues of ccRCC. Ten mRNAs (EPB41L4B, CCND1, GGT1, CGNL1, CYSLTR1, PLAUR, UGT3A1, PROM2, MUC12, and PCK1) were correlated with the overall survival (OS) rate in ccRCC patients based on the GEPIA and ULCAN website.Conclusions: We first reported differentially expressed lncRNAs in ccRCC patient and healthy control systemically. Combined with the published dataset, we identified several differentially expressed lncRNAs and mRNAs which might to be diagnostic or prognostic markers. The biological functions of those lncRNAs and mRNAs should be further validated. Taken together, this study provided the basis for future treatment of ccRCC and novel insights into cancer biology.

Project description:Objective: To analysis lncRNAs expression profiles and identify differentially expressed lncRNAs in CD4+ T cells response to T. pallidum infection in neurosyphilis patients. Methods: CD4+ T cells were isolated from peripheral blood mononuclear cells. RNA extraction was performed to conduct further experiments. Expression profiles of mRNAs and lncRNAs in CD4+ T cells isolated from neurosyphilis patients and healthy controls were analyzed by using microarray assay. Four lncRNAs were selected to conduct validation by using real time-quantitative polymerase chain reaction and the expression levels of those above mentioned lncRNAs in neurosyphilis patients and healthy controls were compared. Results: In total, 17, 278 lncRNAs and 15, 840 mRNA were found to be differentially expressed when comparing the CD4+ T cells between neurosyphilis patients and healthy control individuals. Of these transcripts, 2258 lncRNAs and 1728 mRNAs were significantly over or under expressed, respectively. Compared with healthy controls, AC068282.3 (fold change: 21.90) and CTD-3064M3.3 (fold change: 23.93) were the most over-expressed and under-expressed lncRNAs in neurosyphilis patients. The majority of differentially expressed lncRNAs are from intergenic regions (~ 57.5%), intronic antisense to protein-coding loci (~ 15.0%), natural antisense to protein-coding loci (~12.1%). It is worth noting that 59 lncRNAs were significant difference along with significantly different mRNA. Among the 59 pairs of genes, LOC7999 mRNA was positively correlated with lncRNA RP11-160E2.16, RP11-160E2.11, RP11-160E2.19, respectively; NKX1-1 mRNA was positively correlated with lncRNA RP11-1398P2.1, RP11-160E2.19, XLOC_003422, respectively. The following five mRNAs were correlated with two differential lncRNAs, namely DUSP16, AP000349.1, FAM115C, TIMM8A, SMCHD1. GO analysis revealed that the differentially expressed coding genes were mainly involved in the biological processes, and among them, the most significant association was observed in defense response to fungus, defense response to bacterium, killing cells of other organism and disruption of cells of other organism. Subsequent pathway analysis was also conducted, and T cell receptor signaling pathway, MAPK signaling pathway, TGF-beta signaling pathway, etc. were found out to be associated with differentially expressed mRNAs. Conclusion: The present study revealed the differential expression profiles of lncRNAs in CD4+ T cells response to T. pallidum infection in neurosyphilis patients. LncRNAs are involved in the key biological process in CD4+ T cell response to T. pallidum infection.

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Aberrant lncRNA and mRNA expression in patients with anti-N-methyl-D-aspartate receptor encephalitis

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