Common microRNAs Target Established ASD Genes.
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ABSTRACT:
SUBMITTER: Banerjee-Basu S
PROVIDER: S-EPMC4211397 | biostudies-literature | 2014
REPOSITORIES: biostudies-literature
Publications
Common microRNAs Target Established ASD Genes.
Banerjee-Basu Sharmila S Larsen Eric E Muend Sabina S
Frontiers in neurology 20141028
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Project description:Genetic overlap involving rare disrupting mutations may contribute to high comorbidity rates between autism spectrum disorders and epilepsy. Despite their polygenic nature, genome-wide association studies have not reported a significant contribution of common genetic variation to comorbidity between both conditions. Analysis of common genetic variation affecting specific shared pathways such as miRNA dysregulation could help to elucidate the polygenic mechanisms underlying comorbidity between autism spectrum disorders and epilepsy. We evaluated here the role of common predisposing variation to autism spectrum disorders and epilepsy across target genes of 14 miRNAs selected through bibliographic research as being dysregulated in both disorders. We considered 4,581 target genes from various in silico sources. We described negative genetic correlation between autism spectrum disorders and epilepsy across variants located within target genes of the 14 miRNAs selected (p = 0.0228). Moreover, polygenic transmission disequilibrium test on an independent cohort of autism spectrum disorders trios (N = 233) revealed an under-transmission of autism spectrum disorders predisposing alleles within miRNAs' target genes across autism spectrum disorders trios without comorbid epilepsy, thus reinforcing the negative relationship at the common genetic variation between both traits. Our study provides evidence of a negative relationship between autism spectrum disorders and epilepsy at the common genetic variation level that becomes more evident when focusing on the miRNA regulatory networks, which contrasts with observed clinical comorbidity and results from rare variation studies. Our findings may help to conceptualize the genetic heterogeneity and the comorbidity with epilepsy in autism spectrum disorders.
| S-EPMC10034058 | biostudies-literature
Project description:To gain insights into the in vivo function of miRNAs in the context of periodontitis, we examined the occurrence of miRNAs in healthy and diseased gingival tissues and validated their in silico-predicted targets through mRNA profiling using whole-genome microarrays in the same specimens. Eighty-six individuals with periodontitis contributed 198 gingival papillae: 158 'diseased' (bleeding-on-probing, PD > 4 mm, and AL ? 3 mm) and 40 'healthy' (no bleeding, PD ? 4 mm, and AL ? 2 mm). Expression of 1,205 miRNAs was assessed by microarrays, followed by selected confirmation by quantitative RT-PCR. Predicted miRNA targets were identified and tested for enrichment by Gene Set Enrichment Analysis (GSEA). Enriched gene sets were grouped in functional categories by DAVID and Ingenuity Pathway Analysis. One hundred fifty-nine miRNAs were significantly differentially expressed between healthy and diseased gingiva. Four miRNAs (hsa-miR-451, hsa-miR-223, hsa-miR-486-5p, hsa-miR-3917) were significantly overexpressed, and 7 (hsa-miR-1246, hsa-miR-1260, hsa-miR-141, hsa-miR-1260b, hsa-miR-203, hsa-miR-210, hsa-miR-205*) were underexpressed by > 2-fold in diseased vs. healthy gingiva. GSEA and additional filtering identified 60 enriched miRNA gene sets with target genes involved in immune/inflammatory responses and tissue homeostasis. This is the first study that concurrently examined miRNA and mRNA expression in gingival tissues and will inform mechanistic experimentation to dissect the role of miRNAs in periodontal tissue homeostasis and pathology.
| S-EPMC3446831 | biostudies-literature
Project description:BACKGROUND:Variants of microRNAs (miRNAs), called isomiRs, are commonly reported in deep-sequencing studies; however, the functional significance of these variants remains controversial. Observational studies show that isomiR patterns are non-random, hinting that these molecules could be regulated and therefore functional, although no conclusive biological role has been demonstrated for these molecules. RESULTS:To assess the biological relevance of isomiRs, we have performed ultra-deep miRNA-seq on ten adult human tissues, and created an analysis pipeline called miRNA-MATE to align, annotate, and analyze miRNAs and their isomiRs. We find that isomiRs share sequence and expression characteristics with canonical miRNAs, and are generally strongly correlated with canonical miRNA expression. A large proportion of isomiRs potentially derive from AGO2 cleavage independent of Dicer. We isolated polyribosome-associated mRNA, captured the mRNA-bound miRNAs, and found that isomiRs and canonical miRNAs are equally associated with translational machinery. Finally, we transfected cells with biotinylated RNA duplexes encoding isomiRs or their canonical counterparts and directly assayed their mRNA targets. These studies allow us to experimentally determine genome-wide mRNA targets, and these experiments showed substantial overlap in functional mRNA networks suppressed by both canonical miRNAs and their isomiRs. CONCLUSIONS:Together, these results find isomiRs to be biologically relevant and functionally cooperative partners of canonical miRNAs that act coordinately to target pathways of functionally related genes. This work exposes the complexity of the miRNA-transcriptome, and helps explain a major miRNA paradox: how specific regulation of biological processes can occur when the specificity of miRNA targeting is mediated by only 6 to 11 nucleotides.
| S-EPMC3334621 | biostudies-literature
Project description:We aim to elucidate how miRNAs regulate the mRNA signature of atrial fibrillation (AF), to gain mechanistic insight and identify candidate targets for future therapies. We present combined miRNA-mRNA sequencing using atrial tissues of patient without AF (n = 22), with paroxysmal AF (n = 22) and with persistent AF (n = 20). mRNA sequencing previously uncovered upregulated epithelial to mesenchymal transition, endothelial cell proliferation and extracellular matrix remodelling involving glycoproteins and proteoglycans in AF. MiRNA co-sequencing discovered miRNAs regulating the mRNA expression changes. Key downregulated miRNAs included miR-135b-5p, miR-138-5p, miR-200a-3p, miR-200b-3p and miR-31-5p and key upregulated miRNAs were miR-144-3p, miR-15b-3p, miR-182-5p miR-18b-5p, miR-4306 and miR-206. MiRNA expression levels were negatively correlated with the expression levels of a multitude of predicted target genes. Downregulated miRNAs associated with increased gene expression are involved in upregulated epithelial and endothelial cell migration and glycosaminoglycan biosynthesis. In vitro inhibition of miR-135b-5p and miR-138-5p validated an effect of miRNAs on multiple predicted targets. Altogether, the discovered miRNAs may be explored in further functional studies as potential targets for anti-fibrotic therapies in AF.
| S-EPMC10697892 | biostudies-literature
Project description:To identify target genes of oncogenic or tumor suppressive microRNAs in human cancer, several cell lines (bladder cancer, prostate cancer, renal cell carcinoma. lung squamous cell carcinoma and head and neck squamous cell carcinoma) were subject to Agilent whole genome microarray. miR-183 and miR-96 function as oncogene. miR-1, miR-133a, miR-135a, miR-145 and miR-375 function as tumor suppressor The miRNA transfected human cancer cell lines (KK47, T24, A498, PC3, DU145, FaDu, SAS, PC10 and H157) were compared to control cell lines.
| S-ECPF-GEOD-26032 | biostudies-other
Project description:BackgroundMicroRNAs (miRNAs) are widely studied non-coding RNAs that modulate gene expression. MiRNAs are deregulated in different tumors including gastric cancer (GC) and have potential diagnostic and prognostic implications. The aim of our study was to determine miRNA profile in GC tissues, followed by evaluation of deregulated miRNAs in plasma of GC patients. Using available databases and bioinformatics methods we also aimed to evaluate potential target genes of confirmed differentially expressed miRNA and validate these findings in GC tissues.MethodsThe study included 51 GC patients and 51 controls. Initially, we screened miRNA expression profile in 13 tissue samples of GC and 12 normal gastric tissues with TaqMan low density array (TLDA). In the second stage, differentially expressed miRNAs were validated in a replication cohort using qRT-PCR in tissue and plasma samples. Subsequently, we analyzed potential target genes of deregulated miRNAs using bioinformatics approach, determined their expression in GC tissues and performed correlation analysis with targeting miRNAs.ResultsProfiling with TLDA revealed 15 deregulated miRNAs in GC tissues compared to normal gastric mucosa. Replication analysis confirmed that miR-148a-3p, miR-204-5p, miR-223-3p and miR-375 were consistently deregulated in GC tissues. Analysis of GC patients' plasma samples showed significant down-regulation of miR-148a-3p, miR-375 and up-regulation of miR-223-3p compared to healthy subjects. Further, using bioinformatic tools we identified targets of replicated miRNAs and performed disease-associated gene enrichment analysis. Ultimately, we evaluated potential target gene BCL2 and DNMT3B expression by qRT-PCR in GC tissue, which correlated with targeting miRNA expression.ConclusionsOur study revealed miRNA profile in GC tissues and showed that miR-148a-3p, miR-223-3p and miR-375 are deregulated in GC plasma samples, but these circulating miRNAs showed relatively weak diagnostic performance as sole biomarkers. Target gene analysis demonstrated that BCL2 and DNMT3B expression in GC tissue correlated with their targeting miRNA expression.
| S-EPMC4501563 | biostudies-literature
Project description:BackgroundMicroRNAs play vital role in plant growth and development by changeable expression of their target genes with most plant microRNAs having perfect or near-perfect complementarities with their target genes but miRNAs in Citrus sinensis (csi-miRNAs) and their function have not been widely studied.FindingsIn this study, 15 potential microRNAs in Citrus sinensis (csi-miRNAs) were identified and bioinformatically validated using miR-RACE, a newly developed method for determination of miRNAs prediction computationally. The expression of these fifteen C. sinensis miRNAs can be detected in leaves, stems, flowers and fruits of C. sinensis by QRT-PCR with some of them showed tissue-specific expression. Six potential target genes were identified for six csi-miRNAs and also experimentally verified by Poly (A) polymerase -mediated 3' rapid amplification of cDNA ends (PPM-RACE) and RNA ligase-mediated 5' rapid amplification of cDNA ends (RLM-RACE) which mapped the cleavage site of target mRNAs and detected expression patterns of cleaved fragments that indicate the regulatory function of the miRNAs on their target genes.ConclusionsOur results confirm that small RNA-mediated regulation whereby all csi-miRNAs regulate their target genes by degradation.
| S-EPMC3436860 | biostudies-literature
Project description:Tuberculosis (TB) is the world's most prevalently infectious disease. Molecular mechanisms behind tuberculosis remain unknown. microRNA (miRNA) is involved in a wide variety of diseases. To validate the significant genes and miRNAs in the current sample, two messenger RNA (mRNA) expression profile datasets and three miRNA expression profile datasets were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed (DE) genes (DEGs) and miRNAs (DE miRNAs) between healthy and TB patients were filtered out. Enrichment analysis was executed, and a protein-protein interaction (PPI) network was developed to understand the enrich pathways and hub genes of TB. Additionally, the target genes of miRNA were predicted and overlapping target genes were identified. We studied a total of 181 DEGs (135 downregulated and 46 upregulated genes) and two DE miRNAs (2 downregulated miRNAs) from two gene profile datasets and three miRNA profile datasets, respectively. 10 hub genes were defined based on high degree of connectivity. A PPI network's top module was constructed. The 23 DEGs identified have a significant relationship with miRNAs. 25 critically significant Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were discovered. The detailed study revealed that, in tuberculosis, the DE miRNA and DEGs form an interaction network. The identification of novel target genes and main pathways would aid with our understanding of miRNA's function in tuberculosis progression.
| S-EPMC8572619 | biostudies-literature
Project description:Maize (Zea mays) is an important multi-functional crop. The growth and yield of maize are severely affected by drought stress. Previous studies have shown that microRNAs (miRNAs) in maize play important roles in response to abiotic stress; however, their roles in response to drought stress in maize roots is unclear. In our study, we found 375 miRNAs in the roots of 16 inbred lines. Of the 16 lines, zma-MIR168, zma-MIR156, and zma-MIR166 were highly expressed, whereas zma-MIR399, zma-MIR2218, and zma-MIR2275 exhibited low expression levels. The expression patterns of miRNA in parental lines and their derived RILs are different. Over 50% of miRNAs exhibited a lower expression in recombinant inbred lines than in parents. The expression of 50 miRNAs was significantly altered under water stress (WS) in at least three inbred lines, and the expression of miRNAs in drought-tolerant lines changed markedly. To better understand the reasons for miRNA response to drought, the degree of histone modifications for miRNA genes was estimated. The methylation level of H3K4 and H3K9 in miRNA precursor regions changed more noticeably after WS, but no such phenomenon was seen for DNA methylation and m6A modification. After the prediction of miRNA targets using psRNATarget and psRobot, we used correlation analysis and qRT-PCR to further investigate the relationship between miRNAs and target genes. We found that 87 miRNA-target pairs were significantly negatively correlated. In addition, a weighted gene co-expression network analysis using miRNAs, as well as their predicted targets, was conducted to reveal that miR159, miR394, and miR319 may be related to maize root growth. The results demonstrated that miRNAs might play essential roles in the response to drought stress.
| S-EPMC9104622 | biostudies-literature
Project description:Herpesviruses encode microRNAs (miRNAs) that target both virus and host genes; however, their role in herpesvirus biology is understood poorly. We identified previously eight miRNAs encoded by ovine herpesvirus-2 (OvHV-2), the causative agent of malignant catarrhal fever (MCF), and have now investigated the role of these miRNAs in regulating expression of OvHV-2 genes that play important roles in virus biology. ORF20 (cell cycle inhibition), ORF50 (reactivation) and ORF73 (latency maintenance) each contain predicted targets for several OvHV-2 miRNAs. Co-transfection of miRNA mimics with luciferase reporter constructs containing the predicted targets showed the 5' UTRs of ORF20 and ORF73 contain functional targets for ovhv-miR-2 and ovhv2-miR-8, respectively, and the 3' UTR of ORF50 contains a functional target for ovhv2-miR-5. Transfection of BJ1035 cells (an OvHV-2-infected bovine T-cell line) with the relevant miRNA mimic resulted in a significant decrease in ORF50 and a smaller but non-significant decrease in ORF20. However, we were unable to demonstrate a decrease in ORF73. MCF is a disease of dysregulated lymphocyte proliferation; miRNA inhibition of ORF20 expression may play a role in this aberrant lymphocyte proliferation. The proteins encoded by ORF50 and ORF73 play opposing roles in latency. It has been hypothesized that miRNA-induced inhibition of virus genes acts to ensure that fluctuations in virus mRNA levels do not result in reactivation under conditions that are unfavourable for viral replication and our data supported this hypothesis.
| S-EPMC4820034 | biostudies-literature