miRNA in multiple sclerosis: search for novel biomarkers

Gandhi, Roopali

doi:10.1177/1352458515578771

Cited by 68 publications

(53 citation statements)

References 51 publications

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“…MicroRNAs have been proposed as biomarkers relevant to diagnosis, stage of disease, and response to treatment in MS. 33–35,53 Magnetic resonance imaging techniques have long contributed to the diagnosis and monitoring of the disease. 3 Imaging advances have allowed measurement of heterogeneous pathologic processes, allowing clustering of patients based on these differences.…”

Section: Discussionmentioning

confidence: 99%

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Association Between Serum MicroRNAs and Magnetic Resonance Imaging Measures of Multiple Sclerosis Severity

et al. 2017

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IMPORTANCE MicroRNAs (miRNAs) are promising multiple sclerosis (MS) biomarkers. Establishing the association between miRNAs and magnetic resonance imaging (MRI) measures of disease severity will help define their significance and potential impact. OBJECTIVE To correlate circulating miRNAs in the serum of patients with MS to brain and spinal MRI. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional study comparing serum miRNA samples with MRI metrics was conducted at a tertiary MS referral center. Two independent cohorts (41 and 79 patients) were retrospectively identified from the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital. Expression of miRNA was determined by locked nucleic acid-based quantitative real-time polymerase chain reaction. Spearman correlation coefficients were used to test the association between miRNA and brain lesions (T2 hyperintense lesion volume [T2LV]), the ratio of T1 hypointense lesion volume [T1LV] to T2LV [T1:T2]), brain atrophy (whole brain and gray matter), and cervical spinal cord lesions (T2LV) and atrophy. The study was conducted from December 2013 to April 2016. MAIN OUTCOMES AND MEASURES miRNA expression. RESULTSOf the 120 patients included in the study, cohort 1 included 41 participants (7 [17.1%] men), with mean (SD) age of 47.7 (9.5) years; cohort 2 had 79 participants (26 [32.9%] men) with a mean (SD) age of 43.0 (7.5) years. Associations between miRNAs and MRIs were both protective and pathogenic. Regarding miRNA signatures, a topographic specificity differed for the brain vs the spinal cord, and the signature differed between T2LV and atrophy/destructive measures. Four miRNAs showed similar significant protective correlations with T1:T2 in both cohorts, with the highest for hsa.miR.143.3p

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Section: Discussionmentioning

confidence: 99%

“…30–33 Previous studies have also shown associations between MS disability or disease progression and the expression of miRNAs. 34,35 …”

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confidence: 99%

Association Between Serum MicroRNAs and Magnetic Resonance Imaging Measures of Multiple Sclerosis Severity

et al. 2017

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“…Previous reports of miRNA modulators of both neuronal and immune processes (also termed as NeurimmiRs [36]) predicted therapeutic potential for manipulating miRNA levels in diseases affecting both the immune system and higher brain functions, such as AD [37], Parkinson's disease (PD) [38], multiple sclerosis (MS) [39], anxiety-related disorders [40] and epilepsy [41]. miRNAs primarily target transcriptional or other regulatory genes, which enable modulation of both immune and cognitive processes through direct or indirect alterations of glia-neuron signalling.…”

Section: Discussionmentioning

confidence: 99%

Modulation of miR-146a/complement factor H-mediated inflammatory responses in a rat model of temporal lobe epilepsy

Liu

Meng

et al. 2016

Bioscience Reports

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Increasing evidence supports the involvement of inflammatory and immune processes in temporal lobe epilepsy (TLE). miRNAs represent small regulatory RNA molecules that have been shown to act as negative regulators of gene expression controlling different biological processes, including immune system homoeostasis and function. We investigated the expression and cellular distribution of miRNA-146a (miR-146a) in a rat model of TLE. Prominent up-regulation of miR-146a activation was evident in 1 week after status epilepticus (SE) and persisted in the chronic phase. The predicted miR-146a's target complement factor H (CFH) mRNA and protein expression was also down-regulated in TLE rat model. Furthermore, transfection of miR-146a mimics in neuronal and glial cells down-regulated CFH mRNA and protein levels respectively. Luciferase reporter assays demonstrated that miR-146a down-regulated CFH mRNA expression via 3′-UTR pairing. Down-regulating miR-146a by intracerebroventricular injection of antagomir-146a enhanced the hippocampal expression of CFH in TLE model and decreased seizure susceptibility. These findings suggest that immunopathological deficits associated with TLE can in part be explained by a generalized miR-146a-mediated down-regulation of CFH that may contribute to epileptogenesis in a rat model of TLE.

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“…To date, the most abundantly studied class of these exRNAs are microRNAs (miRNA), which have been implicated in a wide range of diseases including heart failure [1, 2], cancer [3, 4], and multiple sclerosis [5, 6]. miRNAs are small, non-coding RNAs that have the ability to regulate whole networks of genes through transcriptional and translational regulation.…”

Section: Introductionmentioning

confidence: 99%

High Throughput Sequencing of Extracellular RNA from Human Plasma

et al. 2017

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The presence and relative stability of extracellular RNAs (exRNAs) in biofluids has led to an emerging recognition of their promise as ‘liquid biopsies’ for diseases. Most prior studies on discovery of exRNAs as disease-specific biomarkers have focused on microRNAs (miRNAs) using technologies such as qRT-PCR and microarrays. The recent application of next-generation sequencing to discovery of exRNA biomarkers has revealed the presence of potential novel miRNAs as well as other RNA species such as tRNAs, snoRNAs, piRNAs and lncRNAs in biofluids. At the same time, the use of RNA sequencing for biofluids poses unique challenges, including low amounts of input RNAs, the presence of exRNAs in different compartments with varying degrees of vulnerability to isolation techniques, and the high abundance of specific RNA species (thereby limiting the sensitivity of detection of less abundant species). Moreover, discovery in human diseases often relies on archival biospecimens of varying age and limiting amounts of samples. In this study, we have tested RNA isolation methods to optimize profiling exRNAs by RNA sequencing in individuals without any known diseases. Our findings are consistent with other recent studies that detect microRNAs and ribosomal RNAs as the major exRNA species in plasma. Similar to other recent studies, we found that the landscape of biofluid microRNA transcriptome is dominated by several abundant microRNAs that appear to comprise conserved extracellular miRNAs. There is reasonable correlation of sets of conserved miRNAs across biological replicates, and even across other data sets obtained at different investigative sites. Conversely, the detection of less abundant miRNAs is far more dependent on the exact methodology of RNA isolation and profiling. This study highlights the challenges in detecting and quantifying less abundant plasma miRNAs in health and disease using RNA sequencing platforms.

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miRNA in multiple sclerosis: search for novel biomarkers

Cited by 68 publications

References 51 publications

Association Between Serum MicroRNAs and Magnetic Resonance Imaging Measures of Multiple Sclerosis Severity

Association Between Serum MicroRNAs and Magnetic Resonance Imaging Measures of Multiple Sclerosis Severity

Modulation of miR-146a/complement factor H-mediated inflammatory responses in a rat model of temporal lobe epilepsy

High Throughput Sequencing of Extracellular RNA from Human Plasma

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