Large Noncoding RNA in blood

[frodo]

Expression Analysis of Long Non-coding RNAs in the Blood of Multiple Sclerosis Patients.

https://www.ncbi.nlm.nih.gov/pubmed/28967047

Abstract

Multiple sclerosis (MS) is a chronic immune-mediated disorder of the central nervous system (CNS) with multiple genetic and environmental risk factors. Long non-coding RNAs (lncRNAs) have been recently reported to participate in the regulation of immune responses. Consequently, aberrant expression of lncRNAs has been suggested as an underlying cause of MS.

In the present study, we evaluated the expression of three lncRNAs with putative roles in the regulation of immune response, namely TNF-α and heterogeneous nuclear ribonucleoprotein L (THRIL), Fas cell surface death receptor- antisense 1 (FAS-AS1), and plasmacytoma variant translocation 1 (PVT1) in circulating blood cells of 50 Iranian relapsing-remitting multiple sclerosis (RRMS) patients compared with healthy subjects by means of quantitative real-time polymerase chain reaction (PCR).

We detected a significant downregulation of PVT1 and FAS-AS1 expressions in RRMS patients while a significant upregulation of THRIL in patients compared with controls (P < 0.001). Correlation analyses between lncRNA expression levels and clinical data of MS patients revealed no significant correlation between lncRNAs expression levels and Expanded Disability Status Scale (EDSS), a moderate correlation between PVT1 expression levels and duration of the disorder and no significant correlation between lncRNAs expression levels and age at onset. In addition, we demonstrated correlations between the expression levels of PVT1 and THRIL as well as expression levels of THRIL and FAS-AS1 in RRMS patients.

In brief, we have demonstrated dysregulation of three lncRNAs in MS patients. Further studies are needed to explore the exact mechanisms by which these lncRNAs participate in regulation of immune responses.

[Petr75]

2019 Feb 27
Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Integrative analysis of OIP5-AS1/HUR1 to discover new potential biomarkers and therapeutic targets in multiple sclerosis.
https://www.ncbi.nlm.nih.gov/pubmed/30815864

Abstract
Multiple sclerosis (MS) is a devastating autoimmune disease of the central nervous system associated with demyelination and axonal injury. This study was designed to find potential lncRNAs and their targets that are associated with the molecular basis of MS pathogenesis. In this study, peripheral blood samples were obtained from 50 relapsing-remitting MS (RR-MS) patients and 50 healthy controls. lncRNAs and their target were selected for validation using TaqMan Real-Time PCR. Interactions were studied based on approaches that used to investigation biological functions and signaling pathways affected by differentially expressed messenger RNAs (mRNAs). The results of this study indicate an increase in the expression of HUR1 (p = 0.0001), CPSF7 (p = 0.02), and reduction of CSTF2 expression (p = 0.04). Also, an increase in the expression of OIP5-AS1 (p = 0.01) was observed in men less than 30 years old. We performed a comparative analysis of the long noncoding RNAs (lncRNAs), and then we ranked them as candidate biomarkers according to a decreasing area under the receiver operating characteristic (ROC) curve (AUC) and plotted the results. Dysregulation of lncRNA expression has been linked to diseases. Further studies on the HUR1 gene can be used as diagnostic tools for the identification of high-risk individuals in families with a history of disease before, during, and even after treatment. Our data uncovered the expression profiles of lncRNAs and mRNAs in MS patients, which will help delineate the molecular mechanisms in MS pathogenesis. However, further studies need to determine the precise role of these genes in the pathological process in MS.

[Petr75]

2019 May 8
Division of Cellular and Molecular Biology, Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran
Department of Biomedical Sciences, Florida State University, College of Medicine, Tallahassee, Florida
LncRNAs associated with multiple sclerosis expressed in the Th1 cell lineage
https://www.ncbi.nlm.nih.gov/pubmed/31066039

Abstract
Multiple sclerosis (MS) is a type of inflammatory and demyelinating disorder of the central nervous system in which immune-mediated inflammatory processes are elicited by secreted cytokines from T helper (Th)-1 and Th17 cells. While some protein-coding genes expressed in T cell types have established involvement in MS disease progression, little is understood about the roles of long noncoding RNAs (lncRNAs) within the disease landscape. LncRNAs, noncoding RNAs longer than 200 nucleotides, likely control gene expression and function of Th1 cells, and offer the potential to act as therapeutic and biomarker candidates for MS. We identified lncRNAs in Th1 cells linked to MS. Expression levels of candidate lncRNAs and genes were evaluated in 50 MS patients and 25 healthy controls using quantitative real-time polymerase chain reaction, and their correlations were assessed. LncRNAs encoded by AC007278.2 and IFNG-AS1-001 showed significantly higher expression in relapsing Phase MS patients whereas IFNG-AS1-003 was elevated in patients in the remitting phase compared with relapsing patients. Collectively, these misregulated lncRNAs may provide valuable tools to understand the relationships between lncRNAs and MS, and possibly other related disorders.

[Petr75]

2019 Apr 24
Zhejiang Provincial Key Laboratory for Drug Clinical Research and Evaluation, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
Genome-wide identification and analysis of the eQTL lncRNAs in multiple sclerosis based on RNA-seq data.
https://www.ncbi.nlm.nih.gov/pubmed/31323688

Abstract

The pathogenesis of multiple sclerosis (MS) is significantly regulated by long noncoding RNAs (lncRNAs), the expression of which is substantially influenced by a number of MS-associated risk single nucleotide polymorphisms (SNPs). It is thus hypothesized that the dysregulation of lncRNA induced by genomic variants may be one of the key molecular mechanisms for the pathology of MS. However, due to the lack of sufficient data on lncRNA expression and SNP genotypes of the same MS patients, such molecular mechanisms underlying the pathology of MS remain elusive. In this study, a bioinformatics strategy was applied to obtain lncRNA expression and SNP genotype data simultaneously from 142 samples (51 MS patients and 91 controls) based on RNA-seq data, and an expression quantitative trait loci (eQTL) analysis was conducted. In total, 2383 differentially expressed lncRNAs were identified as specifically expressing in brain-related tissues, and 517 of them were affected by SNPs. Then, the functional characterization, secondary structure changes and tissue and disease specificity of the cis-eQTL SNPs and lncRNA were assessed. The cis-eQTL SNPs were substantially and specifically enriched in neurological disease and intergenic region, and the secondary structure was altered in 17.6% of all lncRNAs in MS. Finally, the weighted gene coexpression network and gene set enrichment analyses were used to investigate how the influence of SNPs on lncRNAs contributed to the pathogenesis of MS. As a result, the regulation of lncRNAs by SNPs was found to mainly influence the antigen processing/presentation and mitogen-activated protein kinases (MAPK) signaling pathway in MS. These results revealed the effectiveness of the strategy proposed in this study and give insight into the mechanism (SNP-mediated modulation of lncRNAs) underlying the pathology of MS.

[frodo]

Thanks for the post. I find the last paragraph specially interesting:

These results revealed the effectiveness of the strategy proposed in this study and give insight into the mechanism (SNP-mediated modulation of lncRNAs) underlying the pathology of MS.

Let's hope this time they get the real culprit.

[Petr75]

2019 Aug 6
Department of Cardiovascular Medicine, The Second Hospital Affiliated to Jilin University, Changchun, China
Exosomal long noncoding RNAs in aging and age-related diseases
https://www.ncbi.nlm.nih.gov/pubmed/31386311

Abstract
Molecules secreted by cells into the internal environment during aging, including those secreted in exosomes, have long been a matter of concern. Those cells that absorb exosomes, also known as recipient cells, exhibit certain phenotypic changes because of the regulatory role of functional molecules (including proteins and nucleic acids) released in exosomes. Involvement of noncoding RNAs (ncRNAs) in the regulation of aging has received increasing attention, and long ncRNAs (lncRNAs) have become one of the research hotspots in recent years. LncRNAs carried by exosomes play a role in intercellular communication between adjacent and distant cells. Moreover, exosomal lncRNAs promote the decline of organ functions and the development of age-related diseases, including atherosclerosis, Type 2 diabetes, osteoporosis, osteoarthritis, rheumatoid arthritis, Parkinson's disease, multiple sclerosis, and cancer. Here, we review the regulatory roles of exosomal lncRNAs in aging and age-related diseases.