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Deep sequencing and miRNA profiles in alcohol-induced neuroinflammation and the TLR4 response in mice cerebral cortex

ABSTRACT: Alcohol abuse can induce brain injury and neurodegeneration, and recent evidence shows the participation of immune receptors toll-like in the neuroinflammation and brain damage. We evaluated the role of miRNAs as potential modulators of the neuroinflammation associated with alcohol abuse and the influence of the TLR4 response. Using mice cerebral cortex and next-generation sequencing (NGS), we identified miRNAs that were differentially expressed in the chronic alcohol-treated versus untreated WT or TLR4-KO mice. We observed a differentially expression of miR-183 Cluster (C) (miR-96/-182/-183), miR-200a and miR-200b, which were down-regulated, while mirR-125b was up-regulated in alcohol-treated WT versus (vs.) untreated mice. These miRNAs modulate targets genes related to the voltage-gated sodium channel, neuron hyperexcitability (Nav1.3, Trpv1, Smad3 and PP1-γ), as well as genes associated with innate immune TLR4 signaling response (Il1r1, Mapk14, Sirt1, Lrp6 and Bdnf). Functional enrichment of the miR-183C and miR-200a/b family target genes, revealed neuroinflammatory pathways networks involved in TLR4 signaling and alcohol abuse. The changes in the neuroinflammatory targets genes associated with alcohol abuse were mostly abolished in the TLR4-KO mice. Our results show the relationship between alcohol intake and miRNAs expression and open up new therapeutically targets to prevent deleterious effects of alcohol on the brain.

ORGANISM(S): Mus musculus

PROVIDER: GSE120373 | GEO | 2018/09/25

REPOSITORIES: GEO

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microRNA expression profile in endometrioid endometrial carcinoma (EEC)

Project description:The aim of the presented study was to define tissue and plasma miRNA signatures, which could potentially serve as diagnostic and prognostic markers in endometrioid endometrial cancer (EEC), and to investigate miRNA profiles in regard to clinicopathological characteristics of the tumors. Results: qPCR validation revealed regulation of 14 miRNAs in EEC tissues (miR-9, miR-141,miR-205,miR-203,miR-183,miR-200a*,miR-200b*,miR-200a,miR-200c,miR-429,miR-200b,miR-410,miR-92a,miR-1305) and 9 in plasma samples (miR-449a,miR-1290,miR-1228,miR-203,miR-200a,miR-141,miR-92a, miR-9, miR-301b). Expression of certain miRNAs showed association with FIGO stage, grade and relapse. Two miRNA signatures, miR-205/miR-410 and miR-410/miR-429/miR-92a, classified tumor tissues with higher accuracy in comparison to single miRNAs (AUC 0.972, 95% CI 0.919-0.995 and 0.991, 95% CI 0.948-1.000, resepctively). miRNA signature composed of miR-205 and miR-200a predicted relapse with AUC of 0.854 (95% CI 0.691-0.951). Tissue miRNA signatures were independent prognostic markers of overall (miR-1228/miR-200c/miR-429, HR 2.98) and progression-free survival (miR-1228/miR-429, HR 4.149). Plasma miRNA signatures classified EEC plasma samples with high accuracy. Conclusions: We conclude that miRNA signatures hold great promise for becoming non-invasive biomarkers for early EEC detection and prognosis. Tissue samples were collected from 122 women (77 EEC and 45 controls). Expression profiling of 866 human miRNAs and 89 human viral miRNAs was performed in 24 samples and was followed by qPCR validation in 104 patients. Of 24 samples analyzed by microarrays, 22 (18 EEC, 4 normal controls) were available for final analysis. Expression of 14 miRNAs was analysed in 48 plasma samples by qPCR.

2012-05-31 | E-GEOD-35794 | biostudies-arrayexpress

microRNA expression profile in endometrioid endometrial carcinoma (EEC)

2012-06-01 | GSE35794 | GEO

Gene expression in the human VTA of cases with alcohol abuse

Project description:Drugs of abuse including nicotine and alcohol elicit their effect by stimulating the mesocorticolimbic dopaminergic system. There is a high incidence of nicotine dependence in alcoholics. To date only limited data is available on the molecular mechanism underlying the action of alcohol and nicotine in the human brain. This study utilised gene expression screening to identify genes sensitive to chronic alcohol abuse within the ventral tegmental area of the human brain. Keywords: gene expression, brain, alcohol abuse, human, ventral tegmental area

2007-09-21 | GSE9058 | GEO

The microRNA cluster miR-183/96/182 contributes to long-term memory in a protein phosphatase 1 dependent manner

Project description:Memory formation is a complex cognitive function regulated by coordinated synaptic and nuclear processes in neurons. In mammals, it is controlled by multiple molecular activators and suppressors, including the key signaling regulator protein phosphatase 1 (PP1). Here, we show that memory control by PP1 involves the miR-183/96/182 cluster, which is selectively regulated during memory formation. Inhibiting nuclear PP1 in mice brain or training in object recognition task similarly increases miR-183/96/182 expression in the hippocampus. Mimicking this increase by overexpressing miR-183/96/182 enhances object memory, while suppressing endogenous level of the cluster reduces it. This effect involves the modulation of many plasticity-related genes, and we identified HDAC9 as one of the functional targets. Further, PP1 controls miR-183/96/182 in a transcription-independent manner influencing processing of their precursors. These findings provide novel evidence for the role of miRNAs in memory formation and suggest the implication of PP1 in miRNAs processing in the adult brain.

2016-09-20 | GSE83707 | GEO

microRNA profiles of meningiomas

Project description:Meningiomas, one of the most common human brain tumors, are derived from arachnoidal cells associated with brain meninges, usually benign and frequently associated with neurofibromatosis type 2. Here we define a human meningioma-typical miRNA profile and characterize effects of one down-regulated miRNA, miR-200a, on tumor growth. Elevated levels of miR-200a inhibited meningioma cell growth in culture and in a tumor model in vivo. Up-regulation of miR-200a decreased expression of transcription factors, ZEB1 and SIP1, with consequently increased expression of E-cadherin, an adhesion protein associated with cell differentiation. Down-regulation of miR-200a in meningiomas and arachnoidal cells resulted in increased expression of Î² -catenin and cyclin D1 involved in cell proliferation. miR-200a was found to directly target Î² -catenin mRNA, thereby inhibiting its translation and blocking Î² -catenin-Wnt signaling, frequently involved in cancer. A direct correlation was found between down-regulation of miR-200a and up-regulation of Î²-catenin in human meningioma samples. Thus, miR-200a appears to act as a multi-functional tumor suppressor miRNA in meningiomas through effects on the E-cadherin and Î² -catenin-Wnt signaling pathways. This reveals a previously unrecognized signaling cascade involved in meningioma tumor development and highlights a novel molecular interaction between miR-200a and Wnt signaling, thereby providing insights into novel therapies for meningiomas. 14 meningioma tumor samples were compared to 3 arachnoidal tissue control samples. Two technical replicates were performed for each sample. Normalization and processing included combining the data from technical replicates. The below table contains quantile-normalized data.

2010-06-24 | E-GEOD-17792 | biostudies-arrayexpress

microRNA profiles of meningiomas

Project description:Meningiomas, one of the most common human brain tumors, are derived from arachnoidal cells associated with brain meninges, usually benign and frequently associated with neurofibromatosis type 2. Here we define a human meningioma-typical miRNA profile and characterize effects of one down-regulated miRNA, miR-200a, on tumor growth. Elevated levels of miR-200a inhibited meningioma cell growth in culture and in a tumor model in vivo. Up-regulation of miR-200a decreased expression of transcription factors, ZEB1 and SIP1, with consequently increased expression of E-cadherin, an adhesion protein associated with cell differentiation. Down-regulation of miR-200a in meningiomas and arachnoidal cells resulted in increased expression of β -catenin and cyclin D1 involved in cell proliferation. miR-200a was found to directly target β -catenin mRNA, thereby inhibiting its translation and blocking β -catenin-Wnt signaling, frequently involved in cancer. A direct correlation was found between down-regulation of miR-200a and up-regulation of β-catenin in human meningioma samples. Thus, miR-200a appears to act as a multi-functional tumor suppressor miRNA in meningiomas through effects on the E-cadherin and β -catenin-Wnt signaling pathways. This reveals a previously unrecognized signaling cascade involved in meningioma tumor development and highlights a novel molecular interaction between miR-200a and Wnt signaling, thereby providing insights into novel therapies for meningiomas.

2009-08-25 | GSE17792 | GEO

A MicroRNA Expression Signature For Cervical Cancer Prognosis

Project description:In this study, we have identified a microRNA-based signature for the prediction of cervical cancer survival. MicroRNAs (miRNAs) are a newly identified family of small non-coding RNAs that are extensively involved in human cancers. Using our recently established PCR-based miRNA assays, we have analyzed 102 cervical cancers and identified two miRNAs (miR-200a and miR-9) that are likely to predict patient survival. A logistic regression model was developed based on these two miRNAs and the prognostic value of the model was subsequently validated with 42 independent cervical cancers. Furthermore, functional studies were performed to characterize the effect of miRNAs in cervical cancer cells. Our results suggest that both miR-200a and miR-9 could play important regulatory roles in cervical cancer control. In particular, miR-200a is likely to affect the metastatic potential of cervical cancer cells by simultaneously suppressing the expression of multiple genes that are important to cell motility.

2010-02-15 | GSE18545 | GEO

RNA-Seq of human primary microglial cells treated with vehicle or human paired helical filaments (PHFs) purified from human tauopathy autopsy brain

Project description:Neuroinflammation is one of the major neuropathological hallmarks of Alzheimer's disease (AD) and related tauopathies. Activated microglia often co-exist in the same brain regions where tau protein accumulates as hyperphosphorylated and aggregated PHFs or neurofibrillary tangles (NFTs) within neurons in patients with AD and related tauopathies. However, the exact mechanisms how pathological tau could induce neuroinflammatory responses are not clear. In this study, we treated primary human microglia with purified human PHFs and performed RNA-sequence analysis.

2021-09-16 | E-MTAB-5742 | biostudies-arrayexpress

MiR-200a Regulates CDK4/6 Inhibitor Effect by Targeting CDK6 in Metastatic Melanoma

Project description:Three metastatic melanoma cell lines (BD-0548-ME, DP-0574-ME and WP-0614-ME) were transfected with miR precursors: hsa-miR negative control (NC) or hsa-miR-200a-3p precursors (miR-200a). The objective of this experiment was to determine miR-200a targets in metastatic melanoma cell lines. We selected low -miR-200a expression cell lines and then we overexpressed miR-200a or NC. Finally, we compared the metastatic melanoma cell lines with miR-200a overexpression (miR-200a) to the same cell line transfected with the negative control miR (NC).

2018-06-20 | GSE83512 | GEO

Inhibitory effect of miR-183 on MCM family members

Project description:MYCN and HDAC2 jointly repress the transcription of tumor suppressive micro RNA miR-183 in neuroblastoma. Enforced miR-183 expression induces neuroblastoma cell death and inhibits anchorage-independent colony formation and subcutaneous xenograft growth in mice. We here aimed to unravel the miR-183 signaling network and elucidated the role of MYCN mediated transcriptional activation of members of the minichromosome maintenance (MCM) family protein family involving miR-183 . The hexamer protein complex formed by MCM proteins is involved in the initiation and elongation of eukaryotic genome replication, thereby contributing to genomic integrity. Analysis of miR-183 versus negative control transfected neuroblastoma cells identified 85 differentially expressed proteins in a label-free mass spectrometric approach. Six members of the MCM family were found to be lower expressed upon enforced miR-183 expression, and subsequent annotation category enrichment analysis revealed a 14-fold enrichment in the protein module category “MCM”. Down-regulation was confirmed by western blot analysis. MicroRNA target prediction software studies revealed that miR-183 was predicted to directly target several MCMs.

2016-06-01 | PXD003596 | Pride

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