Global exosome transcriptome profiling reveals biomarkers for multiple sclerosis

Selmaj, Igor; Cichalewska, Maria; Namiecińska, Magdalena; Gałązka, Grażyna; Horzelski, Wojciech; Selmaj, Krzysztof; Mycko, Marcin P.

doi:10.1002/ana.24931

Cited by 146 publications

(125 citation statements)

References 43 publications

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“…MS is thought to result from a complex interplay of genetic, epigenetic, and environmental risk factors . MicroRNAs (miRNAs) are epigenetic factors that have been investigated in MS, and over 170 miRNAs have been found to be differentially expressed in various tissues in either adult‐onset MS or experimental autoimmune encephalomyelitis (EAE) in mice . One study specifically compared miRNA expression levels in ped‐MS cases to pediatric controls, and 12 upregulated and one downregulated miRNA were reported .…”

Section: Introductionmentioning

confidence: 99%

miRNAcontributions to pediatric‐onset multiple sclerosis inferred fromGWAS

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Shao

Graves

et al. 2019

Ann Clin Transl Neurol

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Objective Onset of multiple sclerosis (MS) occurs in childhood for approximately 5% of cases (pediatric MS, or ped‐MS). Epigenetic influences are strongly implicated in MS pathogenesis in adults, including the contribution from microRNAs (miRNAs), small noncoding RNAs that affect gene expression by binding target gene mRNAs. Few studies have specifically examined miRNAs in ped‐MS, but individuals developing MS at an early age may carry a relatively high burden of genetic risk factors, and miRNA dysregulation may therefore play a larger role in the development of ped‐MS than in adult‐onset MS. This study aimed to look for evidence of miRNA involvement in ped‐MS pathogenesis. Methods GWAS results from 486 ped‐MS cases and 1362 controls from the U.S. Pediatric MS Network and Kaiser Permanente Northern California membership were investigated for miRNA‐specific signals. First, enrichment of miRNA‐target gene network signals was evaluated using MIGWAS software. Second, SNPs in miRNA genes and in target gene binding sites (miR−SNPs) were tested for association with ped‐MS, and pathway analysis was performed on associated target genes. Results MIGWAS analysis showed that miRNA‐target gene signals were enriched in GWAS (P = 0.038) and identified 39 candidate biomarker miRNA‐target gene pairs, including immune and neuronal signaling genes. The miR‐SNP analysis implicated dysregulation of miRNA binding to target genes in five pathways, mainly involved in immune signaling. Interpretation Evidence from GWAS suggests that miRNAs play a role in ped‐MS pathogenesis by affecting immune signaling and other pathways. Candidate biomarker miRNA‐target gene pairs should be further studied for diagnostic, prognostic, and/or therapeutic utility.

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Section: Introductionmentioning

confidence: 99%

miRNAcontributions to pediatric‐onset multiple sclerosis inferred fromGWAS

Rhead

Shao

Graves

et al. 2019

Ann Clin Transl Neurol

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“…Laboratory techniques such as quantitative PCR (qPCR), miRNA microarray, and deep sequencing (21) can be used for the early detection of expression profiling of miRNAs. To date, different studies have indicated that miRNA expression profiles could play a role as potential biomarkers for MS (22)(23)(24). Furthermore, miRNAs circulating in plasma have recently been shown to be differentially expressed in different stages of RRMS vs. secondary progressive MS, and they thus have been proposed to be an easily accessible blood-based biomarker to monitor MS (25).…”

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confidence: 99%

Exosome‐associated miRNA profile as a prognostic tool for therapy response monitoring in multiple sclerosis patients

et al. 2018

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Multiple sclerosis (MS) is an autoimmune pathology leading to neurodegeneration. Because of the complexity and heterogenic etiology of this disease, diagnosis and treatment for individual patients are challenging. Exosome-associated microRNAs (miRNAs) have recently emerged as a new class of diagnostic biomarkers involved in both autoimmune and neurologic disorders. Interesting new evidence has emerged showing that circulating miRNAs are dysregulated in MS body fluids, including serum, plasma, and cerebrospinal fluid. We hypothesized that exosome-associated miRNAs could present a readily accessible blood-based assay for MS disease. We detected expression of miRNAs by quantitative PCR on a small cohort of MS patients. We analyzed circulating exosome-associated miRNAs of MS patients before and after therapy and found that 14 exosome-associated miRNAs were significantly down-regulated, while 2 exosome-associated miRNAs were significantly up-regulated in IFN-β-treated relapsing-remitting MS patients with response to therapy compared to those without response. We identified a serum miRNA panel that could be used to monitor the response to IFN-β therapy. Overall, these data suggest that circulating exosome-associated miRNA profiling could represent an easily detectable biomarker of disease and treatment response.-Manna, I., Iaccino, E., Dattilo, V., Barone, S., Vecchio, E., Mimmi, S., Filippelli, E., Demonte, G., Polidoro, S., Granata, A., Scannapieco, S., Quinto, I., Valentino, P., Quattrone, A. Exosome-associated miRNA profile as a prognostic tool for therapy response monitoring in multiple sclerosis patients.

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“…Recently, serum exosomal miRNA profiles of different disease were carried out. The miRNAs present varied greatly between different studies, ranging from 164 serum exosomal miRNAs in cancer patients to 584 distinct miRNAs in serum exosomes per normal sample (19)(20)(21). This phenomenon may be attributed to the different platforms used or to the specific physical environment created by specific diseases or conditions.…”

Section: Discussionmentioning

confidence: 99%

Maternal and umbilical cord serum‐derived exosomes enhance endothelial cell proliferation and migration

et al. 2018

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We investigated the role of exosomes derived from maternal and umbilical cord blood in the regulation of angiogenesis. We report here that both maternal exosomes (MEs) and umbilical exosomes (UEs) significantly enhance HUVEC proliferation, migration, and tube formation. Importantly, ME-treated HUVECs (MEXs) displayed significantly increased migration, but not proliferation or tube formation, compared with UE-treated HUVECs (UEXs). We found that the expression of a subset of migration-related microRNAs (miRNAs), including miR-210-3p, miR-376c-3p, miR-151a-5p, miR-296-5p, miR-122-5p, and miR-550a-5p, among others, were significantly increased or decreased in UEs, and this altered expression was likely correlated with the differential regulation of HUVEC migration. We also found that the mRNA expression of hepatocyte growth factor (HGF) was up-regulated in MEXs and UEXs and, moreover, that inhibiting HGF partially abolished the enhanced cell migration induced by UEs. Our results suggest that both MEs and UEs greatly enhanced endothelial cell (EC) functions and differentially regulated EC migration, which was mostly attributed to the different expression profiles of exosomal miRNA. These findings highlight the importance of exosomes in the regulation of angiogenesis during pregnancy. Exosomal miRNAs, in particular, may be of great significance for the regulation of angiogenesis in maintaining normal pregnancy.-Jia, L., Zhou, X., Huang, X., Xu, X., Jia, Y., Wu, Y., Yao, J., Wu, Y., Wang, K. Maternal and umbilical cord serum-derived exosomes enhance endothelial cell proliferation and migration.

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Global exosome transcriptome profiling reveals biomarkers for multiple sclerosis

Cited by 146 publications

References 43 publications

miRNAcontributions to pediatric‐onset multiple sclerosis inferred fromGWAS

miRNAcontributions to pediatric‐onset multiple sclerosis inferred fromGWAS

Exosome‐associated miRNA profile as a prognostic tool for therapy response monitoring in multiple sclerosis patients

Maternal and umbilical cord serum‐derived exosomes enhance endothelial cell proliferation and migration

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