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LncRNA:mRNA expression profile in CD4+ T cells from patients with Graves' disease.

ABSTRACT: Graves' disease (GD) is a common autoimmune disease that affects the thyroid gland. As a new class of modulators of gene expression, long noncoding RNAs (lncRNAs) have been reported to play a vital role in immune functions and in the development of autoimmunity and autoimmune disease. The aim of this study is to identify lncRNAs in CD4+ T cells as potential biomarkers of GD. lncRNA and mRNA microarrays were performed to identify differentially expressed lncRNAs and mRNAs in GD CD4+ T cells compared with healthy control CD4+ T cells. Quantitative PCR (qPCR) was used to validate the results, and correlation analysis was used to analyze the relationship between these aberrantly expressed lncRNAs and clinical parameters. The microarray identified 164 lncRNAs and 93 mRNAs in GD CD4+ T cells differentially expressed compared to healthy control CD4+ T cells (fold change >2.0 and a P < 0.05). Further analysis consistently showed that the expression of HMlincRNA1474 (P < 0.01) and TCONS_00012608 (P < 0.01) was suppressed, while the expression of AK021954 (P < 0.01) and AB075506 (P < 0.01) was upregulated from initial GD patients. In addition, their expression levels were recovered in euthyroid GD patients and GD patients in remission. Moreover, these four aberrantly expressed lncRNAs were correlated with GD clinical parameters. Moreover, the areas under the ROC curve were 0.8046, 0.7579, 0.8115 for AK021954, AB075506, HMlincRNA1474, respectively. The present work revealed that differentially expressed lncRNAs were associated with GD, which might serve as novel biomarkers of GD and potential targets for GD treatment.

SUBMITTER: Yin Q

PROVIDER: S-EPMC7774754 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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lncRNA:mRNA expression profile in CD4+ T cells from patients with Graves' disease.

Yin Qinglei Q Jin Zhou Z Zhou Yulin Y Song Dalong D Fu Chenyang C Huang FengJiao F Wang Shu S

Endocrine connections 20201201 12

Graves' disease (GD) is a common autoimmune disease that affects the thyroid gland. As a new class of modulators of gene expression, long noncoding RNAs (lncRNAs) have been reported to play a vital role in immune functions and in the development of autoimmunity and autoimmune disease. The aim of this study is to identify lncRNAs in CD4+ T cells as potential biomarkers of GD. lncRNA and mRNA microarrays were performed to identify differentially expressed lncRNAs and mRNAs in GD CD4+ T cells compa ...[more]

PMID: 33112836

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Project description:BackgroundGraves' disease (GD) is one of the most common autoimmune diseases worldwide and develops in 20 to 50 cases per 100,000 persons annually. Long noncoding RNAs (lncRNAs) are widely expressed in multiple human diseases and have pivotal functions in gene regulation. This study is aimed at determining the lncRNA profile in peripheral blood mononuclear cells (PBMCs) from GD patients and investigating the role of ENST00000604491 in GD.MethodsA total of 31 GD patients and 32 normal controls were enrolled in the study. Next-generation sequencing was performed to identify the dysregulated lncRNAs in the PBMCs from the 5 GD patients and 5 normal controls, and 26 GD patients and 27 controls were used to verify the selected lncRNAs. The relative expression of verified lncRNAs, forkhead box P1 (FOXP1), and IKAROS family zinc finger 3 (IKZF3) from these samples was detected by quantitative real-time PCR. The potential biomarker value was assessed by using receiver operating characteristic (ROC) curve analysis.ResultsA total of 37,683 dysregulated expressed lncRNAs were indicated, of which 5 lncRNAs were significantly upregulated and 83 lncRNAs were remarkably downregulated in the GD patients compared with healthy subjects. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that abnormally expressed lncRNAs were mainly enriched in immune system-related signalling pathways. Among the selected lncRNAs, the relative expression of ENST00000604491 was significantly downregulated and negatively correlated with the serum levels of thyroid-stimulating hormone receptor antibodies (TRAb) in GD patients. Further studies confirmed that decreased FOXP1 expression was inversely correlated with serum TRAb levels in GD patients. Moreover, there was a notably positive correlation between ENST00000604491 expression and FOXP1 transcript levels in GD. The area under the ROC curve of ENST00000604491 was up to 0.74 (95% confidence interval: 0.60-0.87, p < 0.01), and the sensitivity and specificity were 53.85% and 88.89%, respectively.ConclusionThe present study identifies ENST00000604491 as a significantly attenuated lncRNA in GD patients, which may contribute to the pathogenesis of GD by regulating FOXP1 and represent a potential biomarker for GD.

Project description:Recent studies have shown that several long noncoding RNAs (lncRNAs) are involved in regulating the immune response to cope with pathogenic invasion. To date, the roles of lncRNAs in the CD4+ T cell response to Treponema pallidum (T. pallidum) infection in neurosyphilis patients remain unknown. The mRNA and lncRNA expression profiles of CD4+ T cells that were isolated from neurosyphilis patients and healthy controls were analyzed by microarray. A total of 2258 lncRNAs and 1728 mRNAs were identified as over-expressed or under-expressed, respectively (fold change > 1.5) in the CD4+ T cells of neurosyphilis patients compared to the healthy controls. The lncRNA-mRNA co-expression network showed that 59 lncRNAs showed significant differences along with significantly different mRNAs. Among the 59 gene pairs, the LOC79999 mRNA was positively correlated with the RP11-160E2.16, RP11-160E2.11, and RP11-160E2.19 lncRNAs, and the NKX1-1 mRNA was positively correlated with the RP11-1398P2.1, RP11-160E2.19, and XLOC_003422 lncRNAs. The following five mRNAs were correlated with two differential lncRNAs: DUSP16, AP000349.1, FAM115C, TIMM8A, and SMCHD1. Gene Ontology (GO) analysis revealed that the differentially expressed coding genes were mainly involved in biological processes and the top 4 terms that associated with above-mentioned differentially expressed coding genes were as follows: defense response to fungus, defense response to bacterium, killing of cells of other organism and disruption of cells of another organism. A subsequent pathway analysis was also conducted, and several pathways, including the T cell receptor, MAPK, and TGF-beta signaling pathways, were associated with the differentially expressed mRNAs. This study reveals the differential expression profiles of lncRNAs in the CD4+ T cell response to the T. pallidum infection in neurosyphilis patients. LncRNAs are involved in key biological processes that comprise the CD4+ T cell response to the T. pallidum infection.

Project description:BackgroundTo explore long-non-coding RNA (lncRNA), microRNA (miRNA) and messenger RNA (mRNA) expression profiles and their biological functions in the urine samples in calcium oxalate (CaOx) patients.MethodsFive CaOx kidney stone patients were recruited in CaOx stone group and six healthy people were included as control group, whose midstream morning urine was collected before the patients were given any medicine on admission. After total RNA was extracted from urine, microarray of miRNA, mRNA and lncRNA were applied to explore their expression variation. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to reveal the gene functions of the dysregulated lncRNA-associated competing endogenous RNA (ceRNA) network. Quantitative real-time PCR were performed on HK-2 cells treated with sodium oxalate (NaOx) to further screen out the differentially expression profiles of these RNAs.ResultsA total of nine miRNAs, 883 mRNAs and 1002 lncRNAs were differentially expressed in urine of CaOx patients compared with normal population. GO analysis revealed that most of mRNAs from ceRNA network were enriched in terms of respiratory burst, regulation of mitophagy, and protein kinase regulator activity. KEGG pathway analysis of these genes related to ceRNA network highlight their critical role in pentose phosphate pathway, glyoxylate and dicarboxylate metabolism, and Janus kinase/signal transducer and activator of transcription (JAK-STAT) signaling pathway. Five miRNAs (miR-6796-3p, miR-30d-5p, miR-3192-3p, miR-518b and miR-6776-3p), four mRNAs (NT5E, CDH4, CLEC14A, CCNL1) and six lncRNAs (lnc-TIGD1L2-3, lnc-KIN-1, lnc-FAM72B-4, lnc-EVI5L-1, lnc-SERPINI1-2, lnc-MB-6) from the HK-2 cells induced by NaOx were consistent with the expression changes of microarray results.ConclusionThe differential expressed miRNAs, mRNAs and lncRNAs may be associated with numerous variations of the signaling pathways or regulation of metabolism and kinase activity, providing potential biomarkers for early diagnosis of urolithiasis and new basis for further research of urolithiasis mechanism.

Project description:Objective: We have already demonstrated that mesenchymal stem cells from patients with ankylosing spondylitis (ASMSCs) exhibited greater adipogenic differentiation potential than those from healthy donors (HDMSCs). Here, we further investigated the expression profile of long noncoding RNA (lncRNA) and mRNA, aiming to explore the underlying mechanism of abnormal adipogenic differentiation in ASMSCs. Methods: HDMSCs and ASMSCs were separately isolated and induced with adipogenic differentiation medium for 10 days. Thereafter, lncRNAs and mRNAs that were differentially expressed (DE) between HDMSCs and ASMSCs were identified via high-throughput sequencing and confirmed by quantitative real-time PCR (qRT-PCR) assays. Then, the DE genes were annotated and enriched by GO analysis. In addition, protein interaction network was constructed to evaluate the interactions between DE mRNAs and to find hub nodes and study cliques. Besides, co-expression network analysis was carried out to assess the co-expressions between DE mRNA and DE lncRNAs, and competing endogenous RNA (ceRNA) network analysis were conducted to predict the relationships among lncRNAs, mRNAs and miRNAs. The signaling pathways based on the DE genes and the predicted DE genes were enriched by KEGG analysis. Results: A total of 263 DE lncRNAs and 1376 DE mRNAs were found during adipogenesis in ASMSCs. qRT-PCR indicated that the expression of the top 20 mRNAs and the top 10 lncRNAs was consistent with the high-throughput sequencing data. Several lncRNAs (NR_125386.1, NR_046473.1 and NR_038937.1) and their target genes (SPN and OR1AIP2), together with the significantly co-expressed pairs of DE lncRNAs and DE mRNAs (SLC38A5-ENST00000429588.1, TMEM61-ENST00000400755.3 and C5orf46-ENST00000512300.1), were closely related to the enhanced adipogenesis of ASMSCs by modulating the PPAR signaling pathway. Conclusion: Our study analyzed the expression profiles of DE lncRNAs and DE mRNAs during adipogenesis in ASMSCs and HDMSCs. Several DE lncRNAs, DE mRNAs and signaling pathways that probably participate in the aberrant adipogenesis of ASMSCs were selected for future study. These results will likely provide potential targets for our intervention on fat metaplasia and subsequent new bone formation in patients with AS in the future.

Project description:Background:Elite controller refers to a patient with human immunodeficiency virus infection with an undetected viral load in the absence of highly active antiretroviral therapy. Studies on gene expression and regulation in these individuals are limited but significant, and have helped researchers and clinicians to understand the interrelationships between HIV and its host. Methods:We collected CD4 T-cell samples from two elite controllers (ECs), two HIV-positive infected patients (HPs), and two healthy controls (HCs) to perform second-generation transcriptome sequencing. Using the Cufflinks software, we calculated the Fragments Per Kilobase of transcript per Million fragments mapped (FPKM) and identified differentially expressed (DE) mRNAs and long non-coding RNAs (lncRNAs), with corrected P value < 0.05 (based on a false discovery rate (FDR) < 0.05). We then constructed a protein-protein interaction network using cytoHubba and a long non-coding RNA-mRNA co-expression network based on the Pearson correlation coefficient. Results:In total, 1109 linear correlations of DE lncRNAs targeting DE mRNAs were found and several interesting interactions were identified as being associated with viral infections and immune responses within the networks based on these correlations. Among these lncRNA-mRNA relationships, hub mRNAs including HDAC6, MAPK8, MAPK9, ATM and their corresponding annotated co-expressed lncRNAs presented strong correlations with the MAPK-NF-kappa B pathway, which plays a role in the reactivation and replication of the virus. Conclusions:Using RNA-sequencing, we systematically analyzed the expression profiles of lncRNAs and mRNAs from CD4+ T cells from ECs, HPs, and HCs, and constructed a co-expression network based on the relationships among DE transcripts and database annotations. This was the first study to examine gene transcription in elite controllers and to study their functional relationships. Our results provide a reference for subsequent functional verification at the molecular or cellular level.

Dataset Information

LncRNA:mRNA expression profile in CD4+ T cells from patients with Graves' disease.

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lncRNA:mRNA expression profile in CD4+ T cells from patients with Graves' disease.

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