Regulation of blood group gene expression by miRNAs
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE76526 | GEO | 2016/01/06
SECONDARY ACCESSION(S): PRJNA307644
REPOSITORIES: GEO
Similar Datasets
Project description:To determine the miRNA expression pattern in RBCs, we isolated miRNA from RBCs of healthy blood donors, who were homozygous or heterozygous carriers of different AB0 blood groups. We first analyzed miRNA expression by microarray chip analysis. In average, we found 873 miRNAs to be present in RBCs with a partially differential expression pattern depending on the blood group genotype. 148 out of these 873 miRNAs were significantly up- or downregulated in RBCs of blood group 0 and of heterozygous genotypes, as compared to homozygous genotypes. For each blood group genotype erythrocyte concentrates of three different donors were used for microarray analysis.
2016-01-06 | E-GEOD-76526 | biostudies-arrayexpress
Project description:Interventions: Patients receive FOLFIRI with bevacizumab fixed 5mg/kg. (Treatment will be continued unless the disease progression, unacceptable toxicity, or consent withdrawal.) Definision of UGT1A1 polymorphisms groups: The homozygous group is patient with homozygous genotype of UGT1A1*28/*28 or UGT1A1*6/*6, with combined heterozygous genotypes of UGT1A1*28 and UGT1A1*6. The heterozygous group is patient with heterozygous genotype of either UGT1A1*28 or UGT1A1*6. The wild group is patients with no UGT1A1*28 and UGT1A1*6 mutation. CPT-11 dosage is wild and heterozygous:CPT-11 150mg/m2 homozygous:CPT-11 100mg/m2
Primary outcome(s): 1)incidence of adverse events 2)frequency of severe toxicity
Study Design: Single arm Non-randomized
| 2620216 | ecrin-mdr-crc
Project description:Interventions: Administraion of CPT-11 is twice for 4 weeks on days 1 and 15. CPT-11 is reconstituted in >=250 mL of normal saline or 5% dextrose in water and infuse 90min on day 1 for pharmacokinetics, and 90min over on day15. CPT-11 adjusted dosage is determined from 50,75,100,125 or 150mg/sqm in the heterozygous group and the homozygous group by continual reassessment method. CPT-11 dosage is fixed at 150mg/sqm in the wild group.Definision of UGT1A1 polymorphisms groups: The homozygous group is patient with homozygous genotype of UGT1A1*28/*28 or UGT1A1*6/*6, with combined heterozygous genotypes of UGT1A1*28 and UGT1A1*6. The heterozygous group is patient with heterozygous genotype of either UGT1A1*28 or UGT1A1*6. The wild group is patients with no UGT1A1*28 and UGT1A1*6 mutation.
Primary outcome(s): Maximum tolerated dose for the heterozygous group and the homozygous group, respectively. Incidence rate of dose limiting toxicities for the wild group.
Study Design: Single arm Non-randomized
| 2616019 | ecrin-mdr-crc
Project description:Background: The number of red blood cells (RBCs) increases significantly in response to high-altitude hypoxic environments, and the RBC microRNA (miRNA) expression pattern is similar to that in whole blood. Studies have shown that miRNA in plasma can act as a circulating hypoxia-associated marker, but the effect of a high-altitude hypoxic environment on RBC-derived miRNAs has not yet been reported. Methods: Blood samples were collected from 20 Han Chinese individuals residing at 500 m (Sichuan Han), 10 migrant Han Chinese citizens residing at 3658 m (Tibet Han) and 12 native Tibetans, and RBC indices measurements and miRNA sequencing analyses were performed for the three sample groups. The levels of some markedly altered miRNAs at high altitude were subsequently measured from 5 randomly selected samples of each group by real-time PCR. Bioinformatic analyses was performed to determine the potential target genes of selected hypoxia-associated miRNAs. Results: Marked changes of several RBC indices were observed among the Tibet Han population, the Tibetan population and the Sichuan Han population. A total of 516 miRNAs derived from RBCs were initially identified by miRNA sequencing in the three sample groups. Compared with the Sichuan Han population, 49 miRNAs were differentially expressed in the Tibet Han population (17 upregulated and 32 downregulated). 12 upregulated and 21 downregulated miRNAs were observed in the Tibetan population compared with the Sichuan Han population. A total of 40 RBC miRNAs were differentially expressed in the Tibetan population (15 upregulated and 25 downregulated) compared with the Tibet Han population. Two significantly altered miRNAs with the highest expression levels (miRNA-144-5p and miR-30b-5p) were selected for real-time PCR analysis, and the results were consistent with those of miRNA sequencing. Furthermore, bioinformatic analyses showed that some potential target genes of miR-144-5p and miR-30b-5p are involved in the erythroid- hypoxia-, and nitric oxide (NO)-related signaling pathways in response to hypoxia. Conclusion: Our findings provide clear evidence, for the first time, that a high-altitude hypoxic environment significantly affects human RBC miRNA profiles.
2018-10-20 | GSE117436 | GEO
Project description:Interventions: Wild-type group:None;Single heterozygous group:None;Mutant homozygous/double heterozygous group:None
Primary outcome(s): Efficacy;The incidence of adverse events
Study Design: Cohort study
| 89703 | ecrin-mdr-crc
Project description:Mature human red blood cells (RBCs) are terminally differentiated anuclear cells. While initially thought to lack any nucleic acids, human RBCs are found to contain abundant and diverse species of RNA transcripts with functional relevance. Given the absence of novel transcription, RBCs may provide an interesting cellular context to study RNA metabolism over time. One clinically relevant context is the ex vivo storage of RBCs in blood banks for use in blood transfusion. Some studies have indicated that the transfusion of “old” or aged stored RBCs may be associated with adverse outcomes due to various storage changes termed “storage lesions”. However, other studies do not support these effects, and much remains unknown about the relevant changes associated with RBC storage. Here, we employed the NanoString nCounter assay for global miRNA profiling to comprehensively define the miRNA turnover during ex vivo RBC storage. This profiling demonstrates that the abundance of most RBC miRNAs did not change significantly during the 42 days of refrigerated storage, indicating extremely long decay half-lives. Unexpectedly, miR-720, a cleavage product of tRNAThr, increased dramatically in the first two weeks and persisted during storage. Furthermore, we present evidence for a role of angiogenin in tRNA cleavage to generate miR-720 during RBC storage. The dramatic increase in miR-720 may serve as a new characteristic for storage lesion and may be used to monitor transfused RBCs in clinical patients and athletes performing blood doping.
2020-05-26 | GSE114990 | GEO
Project description:The callipyge phenotype is a monogenic muscular hypertrophy that is only expressed in heterozygous sheep receiving the CLPG mutation from their sire. The wild-type phenotype of CLPG/CLPG animals is thought to result from translational inhibition of paternally expressed DLK1 transcripts by maternally expressed miRNAs. To identify the miRNA responsible for this trans-effect, we used high-throughput sequencing to exhaustively catalogue miRNAs expressed in skeletal muscle of sheep of the four CLPG genotypes. We have identified 747 miRNA species of which 110 map to the DLK1-GTL2 or callipyge domain. We demonstrate that the latter are imprinted and preferentially expressed from the maternal allele. We show that the CLPG mutation affects their level of expression in cis (~3.2-fold increase) as well as in trans (~1.8-fold increase). In CLPG/CLPG animals, miRNAs from the DLK1-GTL2 domain account for ~20% of miRNAs in skeletal muscle.We show that the CLPG genotype affects the levels of A to I editing of at least five pri-miRNAs of the DLK1-GTL2 domain, but that levels of editing of mature miRNA are always minor. We present suggestive evidence that the miRNAs from the domain target the ORF of DLK1 thereby causing the trans-inhibition underlying polar overdominance. We highlight the limitations of high-throughput sequencing for digital gene expression profiling as a result of biased and inconsistent amplification of specific miRNAs. These data were used to confirm the expression levels found by the high-throughput sequencing analysis. A total of 8 samples (two animals per callipyge genotype) were analysed using the miRCury LNA microRNA array (Exiqon). On each array, the test sample labelled with Hy3 was hybridized on one channel, and a pool made with the 8 test samples (labelled with Hy5) was used on the other channel as a reference for normalization. The callipyge mutation (C) is a SNP localised in an imprinted domain. Thus, heterozygous animals will have different phenotypes. The following 4 genotypes were analyzed in this study: NN: Wild-type (+mat/+pat) CN: Maternal heterozygous (Cmat/+pat) NC: Paternal heterozygous (+mat/Cpat) CC: Homozygous mutant (Cmat/Cpat)
2010-09-24 | E-GEOD-24146 | biostudies-arrayexpress
Project description:Background & Aims. Glycine N-methyltransferase (GNMT) is an essential regulator of the total transmethylation flux in the mammalian liver. Distinct DNA methylation patterns are characteristic of liver development, hepatic de-differentiation and liver disease progression, processes in which the levels of GNMT decrease dramatically by mechanisms still poorly understood. Interestingly, putative binding sites for the microRNA miRNA-873-5p were identified in the 3´UTR of GNMT suggesting a potential role for miRNA-873-5p in GNMT regulation. Results. We have identified that the hepatic expression of miRNA-873-5p was increased in a cohort of cirrhotic and liver cancer patients associated with a down-regulation of GNMT levels. Moreover, during liver development, hepatic de-differentiation and fibrosis, the elevation of miRNA-873-5p coincided with the reduction of GNMT expression, indicating that miRNA-873-5p specifically targets the expression of GNMT. Under these circumstances, inhibition of miRNA-873-5p induced GNMT levels and decreased global CpG methylation and transmethylation flux. Indeed, reestablishment of GNMT expression by miRNA-873-5p inhibition reduced hepatocyte de-differentiation, and abolished completely the mortality produced after bile duct ligation as a result of decreased proinflamatory and profibrogenic markers. miRNA-873-5p knockdown-mediated antifibrotic effect was significantly blunted if its effect on GNMT was blocked. Conclusion. Taken together, our studies highlight the role of miRNA-873-5p as a key regulator of GNMT expression, paving the way for new therapeutical approaches in liver de-differentiation and fibrosis.
2018-12-25 | GSE77840 | GEO
Project description:see publication, arrays from 4 sterile genotypes containing homozygous segments with a Hybrid Male Sterility factor and 1 fertile strain in which the region is a Drosophila simulans and D. mauritiana heterozygous
2011-03-07 | GSE25339 | GEO
Project description:The pupose of this study is to explore tanalysis to investigate the different phenotypes between homozygous and compound heterozygous genotypes in different brain cell types, including patient-specific fibroblasts, iPSCs and iPSCs-derived neural stem cells (NSCs), and astrocytes.
2022-06-28 | GSE207007 | GEO