Identification of miRNA-mRNA regulatory network for Human Atrial Aging [miRNA]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE136926 | GEO | 2019/09/06
REPOSITORIES: GEO
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Project description:We report an integrative analysis of miRNA-seq and mRNA-seq to identify miRNAs, genes, and miRNA-mRNA interactions for human atrial aging (AA). We found that seven miRNAs (4 upregulation and 3 downregulation) and 42 genes (23 upregulation and 19 downregulation) show differential expression between older samples and younger samples in human right atrial tissues. Pearson correlation analysis identified 114 pairs of putative miRNA-mRNA interactions for AA. Pathway enrichment analysis identified three important pathways including rhythmic process, senescence and autophagy in cancer, and positive regulation of cytokine biosynthetic process. Our study revealed novel miRNA-mRNA interaction networks and signaling pathways for AA, providing novel insights into the development of human AA. This dataset includes data generation and processing steps for the mRNA-seq data generated from twelve SR samples.
2019-09-06 | GSE136928 | GEO
Project description:MiRNAs regulate posttranscriptional gene expression and are widely implicated in the pathogenesis of complex diseases. We aim to elucidate miRNA regulation of the atrial mRNA signatures that associate with AF. This may provide novel mechanistical insights and candidate targets for therapies using miRNA mimics or antimiRs.
We present combined miRNAs-mRNAs sequencing in atrial tissues of patient without AF (n=22), with paroxysmal AF (n=22) and with persistent AF (n=20). MiRNA and mRNA signatures followed an ordinal scale from nonAF to paroxysmal to persistent AF patients. The previously reported mRNA sequencing identified 5228 differentially expressed genes involved in epithelial to mesenchymal transition, endothelial cell proliferation and extracellular matrix remodelling involving collagens, glycoproteins and proteoglycans. We discovered 103 differentially expressed miRNAs. 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. The expression levels of differentially expressed miRNAs were negatively correlated with the expression levels of their predicted target mRNAs. The downregulated miRNAs demonstrated a more profound transcriptome effect than the upregulated miRNAs. Upregulated biological processes enriched in miRNAs targets related to epithelial and endothelial cell migration and glycosaminoglycan biosynthesis, in line with the processes discovered by the mRNA sequencing analysis.
Combined analysis of miRNA and mRNA sequencing uncovered miRNAs with a broad transcriptional effect in human AF. Epithelial to mesenchymal transition and endothelial cell proliferation were processes controlled by downregulated miR-135b-5p, miR-138-5p, miR-200a-3p, miR-200b-3p and miR-31-5p, which in turn may contribute to (myo)fibroblast activation and structural remodeling.\
| EGAS00001005296 | EGA
Project description:MicroRNAs (miRNAs) are key players in cancer pathogenesis1. They display differential expression across breast cancer subtypes, and play oncogenic and tumor-suppressive roles2-6. A systematic study of the global miRNA landscape in breast cancer and the factors shaping it has not been undertaken. Here we report the results of profiling miRNA expression in 1,302 breast tumors with detailed clinical annotation and long-term follow-up, and for which matching genomic and mRNA expression data were available7. This provides a comprehensive view of the quantity, distribution and variation of the miRNA population and dissects how much genomic, transcriptional and post-transcriptional events contribute to miRNA expression architecture. The key clinical parameters and cellular pathways related to the miRNA landscape are identified, exemplified by context-dependent interaction with cell adhesion and Wnt signaling. Strikingly, in breast cancer miRNAs appear to act as modulators of mRNA-mRNA interactions rather than molecular switches. We demonstrate an important modulatory role for miRNAs in the biology of breast tumors devoid of somatic copy number aberrations, a common subtype where immune response is prominent. Remarkably, prognostic miRNA signatures derived in this subtype are consistently prognostic across several other subtypes and validate in external cohorts. These findings represent a new framework to study the biology of miRNA in human cancer.
| EGAS00000000122 | EGA
Project description:As the fetal heart develops, cardiomyocyte proliferation potential decreases while fatty acid oxidative capacity increases, a highly regulated transition known as cardiac maturation. Small noncoding RNAs, such as microRNAs (miRNAs), contribute to the establishment and control of tissue-specific transcriptional programs. However, small RNA expression dynamics and genome wide miRNA regulatory networks controlling maturation of the human fetal heart remain poorly understood. Transcriptome profiling of small RNAs revealed the temporal expression patterns of miRNA, piRNA, circRNA, snoRNA, snRNA and tRNA in the developing human heart between 8 and 19 weeks of gestation. Our analysis revealed that miRNAs were the most dynamically expressed small RNA species throughout mid-gestation. Cross-referencing differentially expressed miRNAs and mRNAs predicted 6,200 mRNA targets, 2134 of which were upregulated and 4066 downregulated as gestation progresses. Moreover, we found that downregulated targets of upregulated miRNAs predominantly control cell cycle progression, while upregulated targets of downregulated miRNAs are linked to energy sensing and oxidative metabolism. Furthermore, integration of miRNA and mRNA profiles with proteomes and reporter metabolites revealed that proteins encoded in mRNA targets, and their associated metabolites, mediate fatty acid oxidation and are enriched as the heart develops.This study revealed the small RNAome of the maturing human fetal heart. Furthermore, our findings suggest that coordinated activation and repression of miRNA expression throughout mid-gestation is essential to establish a dynamic miRNA-mRNA-protein network that decreases cardiomyocyte proliferation potential while increasing the oxidative capacity of the maturing human fetal heart.
2024-01-26 | PXD044936 | Pride
Project description:MicroRNA (miRNA) dysregulation is well-documented in psychiatric disease, but miRNA dynamics during adolescent and early adult brain maturation, when symptoms first appear for many of these diseases, remain poorly understood. Here, we use RNA sequencing to examine miRNAs and their mRNA targets in cortex and hippocampus from early, mid-, and late adolescent and adult mice. We also use Quantitative Proteomics by tandem mass tag mass spectrometry (TMT-MS) to examine protein dynamics in cortex from the same subjects.
2023-02-17 | PXD040229 | Pride
Project description:Anaplastic thyroid carcinoma (ATC) is the most fatal and rapidly evolving endocrine malignancy invading the head and neck region and accounting for the majority of thyroid cancer-associated deaths. Deregulation of microRNA (miRNA) expression promotes thyroid carcinoma progression by modulating reorganization of the ATC transcriptome. Here, we applied comparative miRNA-/mRNA-sequencing in a cohort of 28 thyroid carcinomas to unravel the association of deregulated miRNA and mRNA expression. This identifies 85 miRNAs significantly deregulated in ATC. By establishing a new analysis pipeline we unravel 85 prime miRNA-mRNA interactions supporting the downregulation of candidate tumor-suppressors and upregulation of bona fide oncogenes like survivin (BIRC5) in ATC. This miRNA-dependent reprogramming of the ATC transcriptome provides a mRNA signature comprising 65 genes sharply distinguishing ATC from other thyroid carcinomas. Validation of deregulated protein expression in an independent thyroid carcinoma cohort demonstrates that miRNA-dependent oncogenes comprised in this signature, the transferrin receptor TFRC (CD71) and the E3-ubiquitin ligase DTL, are sharply upregulated in ATC. This upregulation is even sufficient to distinguish ATC from partially differentiated thyroid carcinomas (PDTC). In sum, these findings provide new diagnostic tools and a robust resource to explore key miRNA-mRNA regulation underlying the progression of thyroid carcinoma.
2021-11-23 | GSE185719 | GEO
Project description:System level knowledge of host alterations is crucial to elucidate the molecular events of viral pathogenesis and to develop strategies to block viral establishment and amplification. Here, we applied quantitative proteomics approach to study global proteome changes in the host; Spodoptera frugiperda upon infection by a baculovirus, Spodoptera litura NPV at two stages i.e. 12h and 72h post infection. At 12hpi, >95% of host proteins remained stable, however at 72hpi, 52% host proteins exhibited downregulation of 2-fold or more. Functional analysis revealed significant upregulation of transposition and proteasomal machinery while translation, transcription, protein export and oxidative phosphorylation pathways were adversely affected. An assessment of perturbed proteome after viral infection and viral miRNAs expression led to the identification of 117 genes that are potential targets of 10 viral miRNAs. Using miRNA mimics, we confirmed the down regulation of 9 host genes. The results comprehensively show dynamics of host responses after viral infection.
2017-09-25 | PXD005870 | Pride
Project description:To explore the regulatory effect between miRNAs and mRNAs and the possibility of miRNAs as specific blood-based biomarkers in the developmental process of severe alopecia areata (AA), human peripheral blood samples from AA patients and healthy donors were obtained for analysis. we identified 36 significantly differentially expressed miRNAs in severe active AA patients. MiRNA target gene prediction and functional annotation analysis showed a significant enrichment in several pathways including the ribosome, cancer, cell cycle, insulin signaling, TGF-β signaling and p53 signaling pathways. Analysis of the three kinds of network showed that miR-185-5p, miR-125b-5p, and miR-186-5p might play important and synergistic roles in the developmental process of AA. According to the receiver operating characteristic curve analysis, several miRNAs were selected for the quantitative real-time PCR validation and further applied as biomarkers to classify severe active AA patients and healthy individuals. Among the miRNAs, hsa-miR-210 and hsa-miR-1246 had high prediction with high accuracy.
2018-03-01 | GSE93978 | GEO
Project description:Purpose: Identification of miRNA-mRNA interactions in human cells. Method: We used the CLASH technique with PTH-tagged AGO1 protein as a bait. Results: In 6 experiments we identified more than 18,000 miRNA-mRNA interactions in human HEK293 cells, corresponding to targets of 399 miRNAs. Conclusions: The binding of most miRNAs includes the 5' seed region, but around 60% of seed interactions are noncanonical, containing bulged or mismatched nucleotides. Moreover, seed interactions are generally accompanied by specific, non-seed basepairing. 18% of miRNA-mRNA interactions involve the miRNA 3' end, with little evidence for 5' contacts, and some of these were functionally validated. Analyses of miRNA:mRNA basepairing showed that miRNA species systematically differ in their target RNA interactions, and strongly overrepresented motifs were found in the interaction sites of several miRNAs. We speculate that these affect the response of RISC to miRNA-target binding. 6 samples (E1-E6) were prepared with comparable but not identical protocols, described in more detail in Helwak et al. Cell 2013. Samples E7-E10 were used for the determination of the background of the method resulting from RNA-RNA interactions formed after cell lysis.
2013-08-30 | E-GEOD-50452 | biostudies-arrayexpress
Project description:miRNAs are short regulatory single stranded RNA sequences that upon complementary binding to mRNAs lead to the inhibition or degradation of their targets. This regulatory mechanisms has been shown to play crucial roles throughout the whole life cycle of animals and plants as well as in disease. While a plethora of methods exist to predict targets of miRNA, which suggest that up to 80% of the genome is miRNA regulated, it has recently been reported that many of these predictions are false positives, cell type specific or represent non-functional binding. In order to identify the subset of real functional miRNAs and their targets, we established miRNA pathway mutants in mouse embryonic stem cells (mESC), allowing the dissection of canonical and non-canonical functions of pathway members. Additional data integration of downstream regulatory layers (CLIP-seq, ribosome profiling and MS) enabled us to follow and track down real functional miRNA-gene interactions, which reduced the miRNA genome regulation to approximately 1%.
2022-08-31 | PXD014484 | Pride