Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA358056 | ENA |
REPOSITORIES: ENA
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Project description:The molecular response to hypoxia is a critical cellular process implicated in cancer, and a target for drug development. The activity of the major player, HIF1M-NM-1,M-BM- is regulated at different levels, including the transcriptional level by the Ets factor ELK3. The molecular mechanisms of this intimate transcriptional connection remain largely unknown. Whilst investigating global ELK3-chromatin interactions, we uncovered an unexpected connection that involves the microRNA hsa-miR-155-5p, a hypoxia-inducible oncomir that targets HIF1M-NM-1. One of the ELK3 chromatin binding sites, detected by Chromatin Immuno-Precipitation Sequencing (ChIP-seq) of normal Human Umbilical Vein Endothelial Cells (HUVEC), is located at the transcription start site of the MIR155HG genes that expresses hsa-miR-155-5p. We confirmed that ELK3 binds to this promoter by ChIP and QPCR. We showed that ELK3 and hsa-miR-155-5p form a double-negative regulatory loop. ELK3 depletion induced hsa-miR-155-5p expression, and hsa-miR-155-5p expression decreased ELK3 expression at the RNA level through a conserved target sequence in its 3M-bM-^@M-^Y-UTR. We further showed that the activities of hsa-miR-155-5p and ELK3 are functionally linked. Pathway analysis indicates that both factors are implicated in related processes, including cancer and angiogenesis. hsa-miR-155-5p expression and ELK3 depletion have similar effects on expression of known ELK3 target genes, and in-vitro angiogenesis and wound closure. Bioinformatic analysis of cancer RNA-seq data shows that hsa-miR-155-5p and ELK3 expression are significantly anti-correlated, as would be expected from hsa-miR-155-5p targeting ELK3 RNA. Hypoxia (0% oxygen) down-regulates ELK3 mRNA in a microRNA and hsa-miR-155-5p dependent manner. These results tie ELK3 into the hypoxia response pathway through an oncogenic microRNA and into a circuit implicated in the dynamics of the hypoxic response.M-BM- This crosstalk could be important in the development of new treatments for a range of pathologies. Examination of ELK3 DNA interactions in HUVEC cells under normal oxygen conditions
2014-12-04 | E-GEOD-60156 | biostudies-arrayexpress
Project description:Applying Next Generation Sequencing technique we compared the miRNA expression pattern of tumor tissue sample of 6 GPs and peritumoral region of 6 lower grade (I-II) Glioma patients, serving as control group. To determine the difference on miRNA expresion level between GBM and control cases, we performed cluster analysis on the NGS dataset of 6 replicates for each of the two goups of samples with iDEP 96 software. In order to characterize the extent of up- or downregulation, log2FC values were calculated using the iDEP.96 web tool applying the DESeq2 algorithm. On the base of that 117 known miRNAs were identified to be differentially expressed using a threshold of false discovery rate (FDR) <0.05 and fold-change> 2 during the analysis. Among them, 35 miRNAs were upregulated (log2FC > 2) and 82 miRNAs were downregulated (log2FC < -2) with biological revelance in tissue samples comparing with the control samples. To validate our results obtained by NGS, five upregulated miRNAs: hsa-miR-196a-5p, hsa-miR-21-3p, hsa-miR-92b-5p, hsa-miR-10b-3p, hsa-miR-503-5p and three downregulated miRNAs: hsa-mir-383-5p, hsa-mir-490-3p, hsa-mir-1224-3p were chosen for RT-qPCR analysis. As the result of that hsa-miR-196a-5p, hsa-miR-21-3p, and hsa-miR-10b-3p was significantly upregulated while hsa-mir-383-5p and hsa-mir-490-3p was significantly downregulated, compared with those in the control samples. The other three miRNAs: hsa-miR-1224-3p, hsa-miR-92b-5p, hsa-miR-503-5p did not show significant difference between the control group and GPs.
2024-10-31 | GSE244332 | GEO
Project description:Purpose: Given implantation failure limited the improvement of the in vitro fertilization (IVF) success rate, it was urgent to identify potential biomarkers for embryo quality and predicting the outcomes of IVF-ET. Methods: The expression profiles of 16 spent culture media (SCM) collected from embryos at the cleavage on Day 3 (D3 cleavage) and blastocyst stages on Day 5 (D5 blastocyst) during IVF cycles were determined with RNA-sequencing. Differentially expressed miRNAs (DEmiRNAs) were identified with p-value < 0.05 and |log2FC|> 1. Then, the miRNA-mRNA interaction networks were constructed by using Cytoscape software. Finally, the GO and KEGG pathway analysis of target genes of DEmiRNAs were conducted. Results: Compared with pregnant groups, 29 DEmiRNA were detected in non-pregnant groups at D3 cleavage, and 26 DEmiRNA were detected in non-pregnant group at D5 blastocyst. Among them, a total of six known miRNAs, including hsa-miR-199a-3p>hsa-miR-199b-3p, hsa-miR-199a-5p, hsa-miR-379-5p, hsa-miR-432-5p, hsa-miR-99a-5p and hsa-miR-483-5p, were identified. The results of GO and KEGG pathway analysis indicated that these target genes of DEmiRNAs were associated with various biological processes. Conclusion: In conclusion, we identified three miRNAs, including hsa-miR-199a-5p, hsa-miR-483-5p and hsa-miR-432-5p, may serve as biomarkers for embryo quality during IVF cycles.
2023-10-31 | GSE167961 | GEO
Project description:This study aimed to investigate the molecular mechanism responsible for primary open-angle glaucoma (POAG) progression. We analyzed microRNAs (miRNAs) expression profiling in aqueous humor (AH) of both POAG patients and normal controls, using a microarray-based approach. Subsequently, differentially expressed miRNAs (DEmiRNAs) were identified using Bayes moderated t-test. Next, DEmiRNAs target genes were predicted based on miRNA databases, followed by GO analysis and pathway analysis using DAVID. Furthermore, OAG-related genes analysis for target genes was carried out using CTD database, respectively. Finally, verification of DEmiRNAs expression levels was performed by RT-qPCR. A total of 40 significant DEmiRNAs were identified between control and POAG groups, including 24 up-regulated miRNAs and 16 down-regulated miRNAs. Further, the target genes of hsa-miR-206, including BMP2, SMAD4, ID2, and TNF, were mainly enriched in transforming growth factor-β (TGF-β) signaling pathway. While, target genes of hsa-miR-184, hsa-miR-34c-5p, hsa-miR-7-2-3p and hsa-miR-20b-3p, including BCL2, EPHB2, VEGFA, COL4A1, APC, and TGFBR1, were enriched in eye development. Moreover, FNDC3B, CAV2 and VEGF, target genes of hsa-miR-206 or hsa-miR-34c-5p, were the OAG-related genes. Ultimately, RT-qPCR analysis confirmed that mRNA levels of hsa-miR-206, hsa-miR-7-2-3p, and hsa-miR-20b-3p were increased, while those of hsa-miR-184 and hsa-miR-34c-5p were decreased in POAG compared with normal groups (P < 0.05). Hsa-miR-206, hsa-miR-184, hsa-miR-34c-5p, hsa-miR-7-2-3p and hsa-miR-20b-3p might play a significant role in the pathogenesis of POAG and hsa-miR-206 might be associated with the development of POAG by regulating TGF-β signaling pathway. These results might provide insight toward a better understanding of the pathogenesis of POAG.
2015-08-04 | GSE71639 | GEO
Project description:Genome-wide hsa-miR-503, hsa-miR-103, and hsa-miR-494 target profiles [array]
| PRJNA270828 | ENA
Project description:Sequencing of synthetic small RNAs hsa-miR-34b-5p, hsa-miR-449c-5p and their isomir variant
| PRJNA309857 | ENA
Project description:We studied the impact of hsa-miR-139-5p on the protein output by means of an iTRAQ-based approach. First, we established two CAL-62 isogenic cell lines expressing either the mature hsa-miR-139-5p or a non-targeting control upon a doxycycline inducible promoter (PTRE3G-tGFP, Dharmacon). Total proteins of P-tGFP-hsa-miR139-5p untreated or treated with doxycycline (1ug/ml) for 96 and 120 hours were isolated and labeled with iTRAQ® reagent 8-plex. Two independent experiments were performed.
2019-08-13 | PXD011901 | Pride
Project description:The molecular response to hypoxia is a critical cellular process implicated in cancer, and a target for drug development. The activity of the major player, HIF1α, is regulated at different levels, including the transcriptional level by the Ets factor ELK3. The molecular mechanisms of this intimate transcriptional connection remain largely unknown. Whilst investigating global ELK3-chromatin interactions, we uncovered an unexpected connection that involves the microRNA hsa-miR-155-5p, a hypoxia-inducible oncomir that targets HIF1α. One of the ELK3 chromatin binding sites, detected by Chromatin Immuno-Precipitation Sequencing (ChIP-seq) of normal Human Umbilical Vein Endothelial Cells (HUVEC), is located at the transcription start site of the MIR155HG genes that expresses hsa-miR-155-5p. We confirmed that ELK3 binds to this promoter by ChIP and QPCR. We showed that ELK3 and hsa-miR-155-5p form a double-negative regulatory loop. ELK3 depletion induced hsa-miR-155-5p expression, and hsa-miR-155-5p expression decreased ELK3 expression at the RNA level through a conserved target sequence in its 3’-UTR. We further showed that the activities of hsa-miR-155-5p and ELK3 are functionally linked. Pathway analysis indicates that both factors are implicated in related processes, including cancer and angiogenesis. hsa-miR-155-5p expression and ELK3 depletion have similar effects on expression of known ELK3 target genes, and in-vitro angiogenesis and wound closure. Bioinformatic analysis of cancer RNA-seq data shows that hsa-miR-155-5p and ELK3 expression are significantly anti-correlated, as would be expected from hsa-miR-155-5p targeting ELK3 RNA. Hypoxia (0% oxygen) down-regulates ELK3 mRNA in a microRNA and hsa-miR-155-5p dependent manner. These results tie ELK3 into the hypoxia response pathway through an oncogenic microRNA and into a circuit implicated in the dynamics of the hypoxic response. This crosstalk could be important in the development of new treatments for a range of pathologies.
2014-12-04 | GSE60156 | GEO
Project description:Microglia were derived from iPSCs and treated with mimics and inhibitors of the miRNAs hsa-miR-150-5p, hsa-miR-193a-3p and hsa-miR-19b-3p. RNA-sequencing was then performed to examine the effects of up- and down-regulation of the respective miRNAs.
| EGAD00001006842 | EGA
Project description:iPSC-derived neurons were treated with mimics and inhibitors of the miRNAs miR-150-5p, hsa-mir-193a-3p and hsa-miR-19b-3p.
RNA-sequencing was then performed to examine the effects of miRNA up-regulation and inhibition.
| EGAD00001006844 | EGA