MicroRNAs as Novel Regulators of Neuroinflammation

Książek-Winiarek, Dominika; Kacperska, Magdalena Justyna; Głąbiński, Andrzej

doi:10.1155/2013/172351

Cited by 47 publications

(37 citation statements)

References 139 publications

(151 reference statements)

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“…Much attention has been lately given on microglia-dependent inflammasome activation [29, 30], but no data are available on LPS-treated microglia, which is the reason why we assessed the inflammasome multiprotein complex in our model. Once miRNAs are emerging as potent fine-tuners of neuroinflammation [31] and indicated to regulate the inflammatory response when transported in exosomes from primary bone marrow-derived dendritic cells [32], we decided to assess their representation in the LPS-polarized cells and in their derived exosomes to extend our knowledge on such issue, still scarcely explored in microglia primary cultures and unknown in N9 cells. Actually, exosomal miRNAs are currently being extensively studied as biomarkers of disease and the understanding on how they are loaded into exosomes and delivered to specific recipient cells may help in developing therapeutic approaches to modulate innate cell function.…”

Section: Introductionmentioning

confidence: 99%

Exploring New Inflammatory Biomarkers and Pathways during LPS-Induced M1 Polarization

Cunha

Gomes

Vaz

et al. 2016

Mediators of Inflammation

129

109

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Identification of mediators triggering microglia activation and transference of noncoding microRNA (miRNA) into exosomes are critical to dissect the mechanisms underlying neurodegeneration. We used lipopolysaccharide- (LPS-) induced N9 microglia activation to explore new biomarkers/signaling pathways and to identify inflammatory miRNA (inflamma-miR) in cells and their derived exosomes. Upregulation of iNOS and MHC-II (M1-markers) and downregulation of arginase 1, FIZZ1 (M2-markers), and CX3CR1 (M0/M2 polarization) confirmed the switch of N9 LPS-treated cells into the M1 phenotype, as described for macrophages/microglia. Cells showed increased proliferation, activated TLR4/TLR2/NF-κB pathway, and enhanced phagocytosis, further corroborated by upregulated MFG-E8. We found NLRP3-inflammasome activation in these cells, probably accounting for the increased extracellular content of the cytokine HMGB1 and of the MMP-9 we have observed. We demonstrate for the first time that the inflamma-miR profiling (upregulated miR-155 and miR-146a plus downregulated miR-124) in M1 polarized N9 cells, noticed by others in activated macrophages/microglia, was replicated in their derived exosomes, likely regulating the inflammatory response of recipient cells and dissemination processes. Data show that LPS-treated N9 cells behave like M1 polarized microglia/macrophages, while providing new targets for drug discovery. In particular, the study yields novel insights into the exosomal circulating miRNA during neuroinflammation important for emerging therapeutic approaches targeting microglia activation.

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Section: Introductionmentioning

confidence: 99%

Exploring New Inflammatory Biomarkers and Pathways during LPS-Induced M1 Polarization

Cunha

Gomes

Vaz

et al. 2016

Mediators of Inflammation

129

109

View full text Add to dashboard Cite

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“…There are currently over 2,000 annotated human miRNAs that regulate many biological processes, including development, cell proliferation, and organ system homeostasis (Friedlander et al, 2014; Haramati et al, 2010). In the central nervous system, miRNAs are highly expressed, and their dysregulation is linked to several neurodegenerative diseases, including Parkinson’s disease (PD), Alzheimer’s disease (AD), and multiple sclerosis (Goodall et al, 2013; Hartl and Grunwald Kadow, 2013; Ksiazek-Winiarek et al, 2013; Maciotta et al, 2013). Notably, toxicants linked to sALS onset, such as heavy metals and pollution, are also associated with altered miRNA expression (Ahmed and Wicklund, 2011; Callaghan et al, 2011; Wang and Cui, 2012), and two fALS genes, fused in sarcoma ( FUS ) and transactive response DNA binding protein 43 ( TARDBP ) encoding the TDP-43 protein, are involved in RNA processing and miRNA biogenesis (Buratti et al, 2010; Kawahara and Mieda-Sato, 2012; Mackenzie et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Expression of microRNAs in human post-mortem amyotrophic lateral sclerosis spinal cords provides insight into disease mechanisms

Figueroa‐Romero

Hur

Lunn

et al. 2016

Molecular and Cellular Neuroscience

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Amyotrophic lateral sclerosis is a late-onset and terminal neurodegenerative disease. The majority of cases are sporadic with unknown causes and only a small number of cases are genetically linked. Recent evidence suggests that post-transcriptional regulation and epigenetic mechanisms, such as microRNAs, underlie the onset and progression of neurodegenerative disorders; therefore, altered microRNA expression may result in the dysregulation of key genes and biological pathways that contribute to the development of sporadic amyotrophic lateral sclerosis. Using systems biology analyses on postmortem human spinal cord tissue, we identified dysregulated mature microRNAs and their potential targets previously implicated in functional process and pathways associated with the pathogenesis of ALS. Furthermore, we report a global reduction of mature microRNAs, alterations in microRNA processing, and support for a role of the nucleotide binding protein, TAR DNA binding protein 43, in regulating sporadic amyotrophic lateral sclerosis-associated microRNAs, thereby offering a potential underlying mechanism for sporadic amyotrophic lateral sclerosis.

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“…miRNAs affect gene expression through interaction between their seed region and the 3′-or 5′-untranslated region (UTR) of the target mRNA [11], which leads to mRNA cleavage, translational repression or activation, and the formation of heterochromatin [12]. Numerous studies have shown that different miRNAs in cancer might function either as activators or suppressors of tumors through regulation of different targets.…”

Section: Introductionmentioning

confidence: 99%

miR-125a-3p targets MTA1 to suppress NSCLC cell proliferation, migration, and invasion

Zhang¹,

Zhu²,

Li³

et al. 2015

ABBS

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Metastasis-associated gene 1 (MTA1) is associated with cell growth, metastasis, and survival in nonsmall-cell lung cancer (NSCLC). Several previous reports have demonstrated that microRNAs affect gene expression through interaction between their seed region and the 3′-untranslated region of the target mRNA, resulting in post-transcriptional regulation. The aim of this study was to identify miRNAs that suppress malignancy in NSCLC cells by targeting MTA1. Two human NSCLC cell lines were analyzed for the expression of MTA1 by quantitative RT-PCR and western blotting after transfection with MTA1 mimics. A luciferase reporter assay was established to test the direct connection between MTA1 and its upstream miRNAs. Cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, 5-ethynyl-2′-deoxyuridine analysis, and colony formation assay. Cell migration and invasive capacity were evaluated by wound-healing assay and transwell assay. The miRNA/MTA1 axis was also probed by quantitative RT-PCR and western blotting in samples from eight NSCLC patients. Among the candidate miRNAs, miR-125a-3p was shown to posttranscriptionally regulate MTA1 in NSCLC cells. These data were reinforced by the luciferase reporter assay, in addition to the demonstration that MTA1 is inversely correlated with miR-125a-3p in NSCLC tissues. Furthermore, miR-125a-3p was found to inhibit NSCLC cell proliferation, migration, and invasion, through the same mechanisms of down-regulated MTA1. Our report demonstrates that miR-125a-3p inhibits the proliferation, migration, and invasion of NSCLC cells through down-regulation of MTA1, indicating the role of the miR-125a-3p/MTA1 axis in NSCLC, and may provide novel insight into the molecular mechanisms underpinning the disease and potential therapeutic targets.

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MicroRNAs as Novel Regulators of Neuroinflammation

Cited by 47 publications

References 139 publications

Exploring New Inflammatory Biomarkers and Pathways during LPS-Induced M1 Polarization

Exploring New Inflammatory Biomarkers and Pathways during LPS-Induced M1 Polarization

Expression of microRNAs in human post-mortem amyotrophic lateral sclerosis spinal cords provides insight into disease mechanisms

miR-125a-3p targets MTA1 to suppress NSCLC cell proliferation, migration, and invasion

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