Deep sequencing analysis of miRNAs and isomiRs modulated by long-term exposure of human endothelial cells to metformin
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ABSTRACT:
PROVIDER: PRJNA630079 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11682464.fastq.gz | Fastqsanger.gz | |||
| SRR11682465.fastq.gz | Fastqsanger.gz | |||
| SRR11682466.fastq.gz | Fastqsanger.gz | |||
| SRR11682467.fastq.gz | Fastqsanger.gz | |||
| SRR11682468.fastq.gz | Fastqsanger.gz |
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Project description:Increasing evidence suggest anti-senescence and geroprotective roles for the glucose-lowering drug metformin. In this framework, the ability of metformin to affect the biogenesis of selected microRNAs (miRNAs) was recently suggested. IsomiRs are distinct variations of miRNA sequences, such as addition or deletion of one or more nucleotides at the 5’ and/or 3’ ends of the canonical miRNA sequence. Since no study has comprehensively assessed the miRNA signatures, including isomiR variants, affected by metformin treatment during cellular senescence, we analysed miRNA and isomiR expression in human umbilical vein endothelial cells (HUVECs) undergoing replicative senescence in presence of metformin.
2020-12-03 | GSE149771 | GEO
Project description:Circulating small RNAs. including miRNAs but also isomiRs and other RNA species. have the potential to be used as non-invasive biomarkers for communicable and non-communicable diseases. This study aims to characterize miRNAs. isomiRs and small RNA clusters in biofluids. to compare their profiles. and to help in the establishment of standard guidelines. For this purpose. RNA from plasma and breast milk samples from 15 healthy postpartum mothers was extracted. Small RNA libraries were prepared with the NEBNext® small RNA library preparation kit and sequenced in an Illumina HiSeq2000 platform. After an initial quality control. miRNAs. isomiRs and clusters of small RNAs were annotated using seqBuster/seqCluster framework. The average amount of extracted RNA was 81 ng/mL [standard deviation (SD): 41] and 3985 ng/mL (SD: 3767) for plasma and breast milk. respectively. Mean number of good quality reads was 4.04 million (M) (40.01% of the reads) in plasma and 12.5M (89.6%) in breast milk. One thousand one hundred eighty two miRNAs. 74.317 isomiRs and 1.053 small RNA clusters that included piwi-interfering RNAs (piRNAs). tRNAs. small nucleolar RNAs (snoRNA) and small nuclear RNAs (snRNAs) were detected. Samples grouped by biofluid. with 308 miRNAs. 4.737 isomiRs and 778 small RNA clusters differentially detected. In summary. plasma and milk showed a completely different small RNA profile. In both. miRNAs. piRNAs. tRNAs. snRNAs. and snoRNAs were identified. confirming the presence of non-miRNA species in biofluids
2018-03-14 | GSE107524 | GEO
Project description:Increasing evidence suggest that the glucose-lowering drug metformin exerts a valuable anti-senescence role. The ability of metformin to affect the biogenesis of selected microRNAs (miRNAs) was recently suggested. MicroRNA isoforms (isomiRs) are distinct variations of miRNA sequences, harboring addition or deletion of one or more nucleotides at the 5' and/or 3' ends of the canonical miRNA sequence. We performed a comprehensive analysis of miRNA and isomiR profile in human endothelial cells undergoing replicative senescence in presence of metformin. Metformin treatment was associated with the differential expression of 27 miRNAs (including miR-100-5p, -125b-5p, -654-3p, -217 and -216a-3p/5p). IsomiR analysis revealed that almost 40% of the total miRNA pool was composed by non-canonical sequences. Metformin significantly affects the relative abundance of 133 isomiRs, including the non-canonical forms of the aforementioned miRNAs. Pathway enrichment analysis suggested that pathways associated with proliferation and nutrient sensing are modulated by metformin-regulated miRNAs and that some of the regulated isomiRs (e.g. the 5' miR-217 isomiR) are endowed with alternative seed sequences and share less than half of the predicted targets with the canonical form. Our results show that metformin reshapes the senescence-associated miRNA/isomiR patterns of endothelial cells, thus expanding our insight into the cell senescence molecular machinery.
| S-EPMC7732983 | biostudies-literature
Project description:Variants of microRNAs, (isomiRs) are commonly reported in deep-sequencing studies; however the functional significance of these variants remains controversial. To assess their biological relevance, we have performed ultra-deep miRNA-seq on ten adult human tissues, and created an analysis pipeline (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. We isolated polyribosome-associated mRNA, and 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 showed substantial overlap in functional mRNA networks suppressed by both canonical miRNAs and their isomiRs. Together, these results find isomiRs to be biologically relevant and functionally synergistic 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 with predominantly non-specific miRNA-mRNA interactions.
2011-12-21 | GSE29043 | GEO
Project description:Purpose: In testis the effects of exposure to mixtures of Endocrine disruptors compounds (EDCs) upon expression of miRNAs were not addressed. Objective: To identify the expression profiles of the 'miRNome' in mice testis chronic exposed to a defined mixture of five EDCs. Methods: Pregnant mice from 0.5 post-coital day were exposed in the drinking water to a mixture containing 0.3 mg/Kg-bw/day of each phthalate (DEHP, DBP, BBP), plus 0.05 mg/Kg-bw/day of each alkylphenol (NP, OP) until adulthood of male mouse (60 days old). We characterized the 'miRNome' by next generation sequence (NGS). Results: In mouse testis exposed to EDCs mixture we detected by NGS 2 up-regulated and 8 down-regulated miRNAs along to 36 isomiRs differentially expressed; these results were validated by RT-qPCR. and functional analysis showed deregulation of testicular hormonal status, spermatogenesis disruption and germ cells apoptosis. Conclusions: Here we provide the first association between deregulation of miRNAs, isomiRs, with histopathological and hormonal alterations in adult mice testis exposed to mixture of EDCs.
2017-07-31 | GSE84695 | GEO
Project description:This data set is part of a larger study: Variants of microRNAs, (isomiRs) are commonly reported in deep-sequencing studies; however the functional significance of these variants remains controversial. To assess their biological relevance, we have performed ultra-deep miRNA-seq on ten adult human tissues, and created an analysis pipeline (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. We isolated polyribosome-associated mRNA, and 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 showed substantial overlap in functional mRNA networks suppressed by both canonical miRNAs and their isomiRs. Together, these results find isomiRs to be biologically relevant and functionally synergistic 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 with predominantly non-specific miRNA-mRNA interactions.
2011-12-21 | GSE29100 | GEO
Project description:Variants of microRNAs, (isomiRs) are commonly reported in deep-sequencing studies; however the functional significance of these variants remains controversial. To assess their biological relevance, we have performed ultra-deep miRNA-seq on ten adult human tissues, and created an analysis pipeline (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. We isolated polyribosome-associated mRNA, and 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 showed substantial overlap in functional mRNA networks suppressed by both canonical miRNAs and their isomiRs. Together, these results find isomiRs to be biologically relevant and functionally synergistic 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 with predominantly non-specific miRNA-mRNA interactions. HEK293T cells were transfected with biotinylated miRNAs (either mir-10a-iso, mir-10a, mir-10b-iso or mir-10b) or a mock control. The miRNAs and target mRNA were pulled down with streptavidin. The pulled down RNA was hybridised to Illumina microarrays. The miRNA-Seq data have been submitted to the short read archive under SRA number SRP006043: http://www.ncbi.nlm.nih.gov/sra?term= SRP006043
2011-12-21 | E-GEOD-29043 | biostudies-arrayexpress
Project description:This data set is part of a larger study: Variants of microRNAs, (isomiRs) are commonly reported in deep-sequencing studies; however the functional significance of these variants remains controversial. To assess their biological relevance, we have performed ultra-deep miRNA-seq on ten adult human tissues, and created an analysis pipeline (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. We isolated polyribosome-associated mRNA, and 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 showed substantial overlap in functional mRNA networks suppressed by both canonical miRNAs and their isomiRs. Together, these results find isomiRs to be biologically relevant and functionally synergistic 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 with predominantly non-specific miRNA-mRNA interactions. 6 samples submitted, all replicates of Human Placenta total RNA, Ambion The miRNA-Seq data have been submitted to the short read archive under SRA number SRP006043: http://www.ncbi.nlm.nih.gov/sra?term= SRP006043
2011-12-21 | E-GEOD-29100 | biostudies-arrayexpress
Project description:Circulating miRNAs. isomiRs and small RNA clusters in human plasma and breast milk
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Project description:The biguanide drug metformin is a safe and widely prescribed drug for type 2 diabetes. Interestingly, hundreds of clinical trials were set to evaluate the potential role of metformin in the prevention and treatment of cancer including colorectal cancer (CRC). However, the metformin-induced cell signaling remains controversial. To interrogate cell signaling events and networks in CRC and explore the druggability of the metformin-rewired phosphorylation network, we performed a proteomic and phosphoproteomic analysis on a panel of 12 molecularly heterogeneous CRC cell lines. Using in-depth data-independent analysis mass spectrometry (DIA-MS), we profiled a total of 10,142 proteins and 56,080 phosphosites (P-sites) in CRC cells treated with metformin for 30 minutes and 24 hours. Our results indicate that metformin tends to not trigger or inhibit significant immediate phosphorylation events. Instead, it primarily remodels cell signaling in the long-term. Strikingly, the phosphorylation response to metformin was highly heterogeneous in the CRC panel. We further performed a network analysis to systematically estimate kinase/phosphatase activities and reconstruct signaling cascades in each cell line. We created a “MetScore” which catalogs the most consistently perturbed P-sites among CRC cells for future studies. Finally, we leveraged the metformin P-site signature to identify pharmacodynamic interactions, revealing and confirming a number of candidate metformin-interacting drugs, including navitoclax, a BCL-2/BCL-xL inhibitor. Together, we provide a state-of-the-art phosphoproteomic resource to explore the metformin-induced cell signaling for potential cancer therapeutics.
2023-02-18 | PXD036826 | Pride