The Emerging Functions of Long Noncoding RNA in Immune Cells: Autoimmune Diseases

Sigdel, Keshav Raj; Cheng, Antony S.; Wang, Yin; Duan, Lihua; Zhang, Yanlin

doi:10.1155/2015/848790

Cited by 127 publications

(113 citation statements)

References 69 publications

(92 reference statements)

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“…T cells, dentritic cells, B cells, macrophages and NK cells [24]. Emerging evidence indicates that lncRNAs not only participate in autoimmune diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and psoriasis [25-27], but also play important roles in CNS development, homeostasis, stress responses, and plasticity [28]. Recent work points to the role of lncRNAs in oligodendrocyte precursor cell (OPC) differentiation from neural stem cells (NSCs), myelination and remyelination in the CNS [29, 30].…”

Section: Discussionmentioning

confidence: 99%

Analysis of Long Noncoding RNA and mRNA Expression Profiles in IL-9-Activated Astrocytes and EAE Mice

Liu

Zhang

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Multiple sclerosis (MS) is an autoimmune disease in the central nervous system associated with demyelination and axonal injury. Astrocyte activation is involved in the pathogenesis of MS and experimental autoimmune encephalomyelitis (EAE), an animal model of MS. This study was designed to find potential lncRNAs in EAE mice and activated astrocytes. Methods: we performed microarray analysis of lncRNAs from the brain tissues of EAE mice and primary mouse astrocytes treated with IL-9(50 ng/ml). 12 lncRNAs were validated through real-time PCR. Gene ontology and KEGG pathway analysis were applied to explore the potential functions of lncRNAs. Results: Differentially expressed 3300 lncRNAs and 3250 mRNAs were in the brain tissues of EAE mice, and 3748 lncRNAs and 3332 mRNAs were in activated astrocytes. Notably, there were 2 co-up-regulated lncRNAs and 3 co-down-regulated lncRNAs both in the brain tissues of EAE mice and in activated astrocytes, including Gm14005, Gm12478, mouselincRNA1117, AK080435, and mouselincRNA0681, which regulate the ER calcium flux kinetics, zinc finger protein and cell apoptosis. Similarly, there were 7 mRNAs co-up-regulated and 2 mRNAs co-down-regulated both in vivo and in vitro. Gene ontology and KEGG pathway analysis showed that the biological functions of differentially expressed mRNAs were associated with metabolism, development and inflammation. The results of realtime PCR validation were consistent with the data from the microarrays. Conclusions: Our data uncovered the expression profiles of lncRNAs and mRNAs in vivo and in vitro, which may help delineate the mechanisms of astrocyte activation during MS/EAE process.

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Section: Discussionmentioning

confidence: 99%

Analysis of Long Noncoding RNA and mRNA Expression Profiles in IL-9-Activated Astrocytes and EAE Mice

Liu

Zhang

Wang

et al. 2018

Cell Physiol Biochem

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“…LncRNAs are also associated with many human diseases, such as prostate cancer, breast cancer, and Alzheimer's disease [181]. Recent studies provide evidence that lncRNAs participate in autoimmune diseases including SLE, RA, and psoriasis [182]. Coincidently, X-inactive-specific transcript (Xist) is one of the first discovered lncRNA in mammals [183,179], which implies an important role in female preponderance of autoimmune disease at the epigenetic level.…”

Section: Long Noncoding Rnamentioning

confidence: 99%

Epigenetics and Primary Biliary Cirrhosis: a Comprehensive Review and Implications for Autoimmunity

Xie

Lian

2015

Clinic Rev Allerg Immunol

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Primary biliary cirrhosis (PBC) is a chronic inflammatory autoimmune disease that develops based upon the interaction of genetic and environmental factors. Recent genome-wide association studies (GWAS) have identified dozens of predisposing variants including HLA, IL12A, and CTLA4 but have been disappointed in identifying a "smoking gun." These discoveries highlight the importance of the genetic background involved in immunological dysregulation. Although concordance rate of PBC in monozygotic (MZ) twins is among the highest reported in autoimmune disorders, incomplete disease concordance in twins associated with differentially expressed genes has been demonstrated. However, little is understood about how environmental aspects contribute to the disease and why middle-aged women are more susceptible. As a result, epigenetic factors, which convert signals indicating environmental changes into dynamic and heritable alterations of transcriptional potential, are getting increased attention by researchers in both basic and clinical studies. Among epigenetic mechanisms, the instability and skewed gene expression in the X chromosome may account for the female preponderance in PBC. In addition, transcriptional regulation of histone modification and DNA methylation underscores potential involvement in disease pathogenesis. High-throughput techniques are being used to identify epigenetic regulators. In this review, we attempt to outline recent progress regarding epigenetics in PBC and other autoimmune diseases.

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“…LncRNAs have been shown to affect every stage of a gene's life cycle, including chromosome reconstruction, transcription, post-transcription, and intracellular metabolism [15][16][17][18]. In a recent study, the role of lncRNAs in the development of autoimmune diseases was highlighted [19]. For example, the lncRNAs, Gas5, Hotair and H19, and Tmevg1, have roles in systemic lupus erythematosus (SLE) [20,21], rheumatoid arthritis (RA) [22,23], and Sjögren syndrome (SS) [24], respectively.…”

Section: Introductionmentioning

confidence: 99%

Abnormal Expression of Long Noncoding RNAs in Primary Immune Thrombocytopenia: A Microarray Related Study

Liu

et al. 2018

Cell Physiol Biochem

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Background/Aims: Long noncoding RNAs (lncRNAs) are important regulators of biological processes and they contribute to the pathological developments of various diseases, including autoimmune diseases. To gain the further understanding, we estimate the expression of lncRNAs in primary immune thrombocytopenia (ITP). Methods: In this study, microarray studies were performed to characterize expression profiles of various lncRNAs and mRNAs in blood samples collected from ITP patients. Quantitative real-time PCR (qRT-PCR) was performed to confirm the results, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and gene ontology analysis were used to provide functional annotations, co-expression network construction (CNC) analysis was made to reveal the relations between lncRNAs and their targeted genes. Results: A total of 1177 and 632 lncRNAs were significantly up-regulated or down-regulated, respectively, in “newly diagnosed ITP” patients versus healthy individuals. In addition, 1182 genes and 737 genes were up-regulated or down-regulated, respectively, in “chronic recurrent ITP” patients versus healthy individuals. In a KEGG analysis, “TNF signaling pathway-Homo sapiens (human)” was a key result. In a gene ontology analysis, “Granulocyte macrophage colony-stimulating factor production (GO: 0032604, ontology: Biological process, P = 1.69577E-05)” and “coreceptor activity (GO: 0015026, ontology: molecular function, P = 4.67594E-06)” were the two most critical results. Data from qRT-PCR and receiver operating characteristic curves further demonstrated that ENST00000440492, ENST00000528366, NR_038920, and ENST00000552576 can efficiently distinguish different stages of ITP, especially NR_038920 and ENST00000528366. In a CNC analysis, four lncRNAs were emphasized, and NR_038920 and ENST00000528366 were both associated with proteins with important roles in autoimmune diseases. Conclusions: These results suggest that lncRNAs act through targeted genes to mediate their functions and to mediate their functions and affect the pathogenesis of ITP.

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The Emerging Functions of Long Noncoding RNA in Immune Cells: Autoimmune Diseases

Cited by 127 publications

References 69 publications

Analysis of Long Noncoding RNA and mRNA Expression Profiles in IL-9-Activated Astrocytes and EAE Mice

Analysis of Long Noncoding RNA and mRNA Expression Profiles in IL-9-Activated Astrocytes and EAE Mice

Epigenetics and Primary Biliary Cirrhosis: a Comprehensive Review and Implications for Autoimmunity

Abnormal Expression of Long Noncoding RNAs in Primary Immune Thrombocytopenia: A Microarray Related Study

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