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A set of circulating microRNAs belonging to the 14q32 chromosomic locus identifies two different subgroups of individuals with recent onset Stage 3 type 1 diabetes [first cohort, targeted]

ABSTRACT: Circulating microRNAs are linked to the onset and progression of type 1 diabetes mellitus (T1DM), making them potential biomarkers for the disease. In this study, we employ a multiplatform sequencing approach to analyze circulating microRNAs in an extended cohort of individuals with T1DM from the INNODIA consortium. Our findings reveal that a set of microRNAs located within the T1DM susceptibility chromosomal locus 14q32 distinguishes two subgroups of individuals. To validate our results, we conduct additional analyses on a second cohort of T1DM individuals, confirming the identification of these subgroups, which we have named Cluster A and Cluster B. Remarkably, Cluster B T1DM individuals, who exhibit increased expression of a set of 14q32 miRNAs, show better glycaemic control and display a different blood immunomics profile. Our findings suggest that this set of circulating microRNAs can identify two different T1DM subgroups with distinct blood immunomics at baseline and clinical outcomes during follow-up.

ORGANISM(S): Homo sapiens

PROVIDER: GSE265976 | GEO | 2024/05/03

REPOSITORIES: GEO

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A set of circulating microRNAs belonging to the 14q32 chromosomic locus identifies two different subgroups of individuals with recent onset Stage 3 type 1 diabetes [second cohort, untargeted]

Project description:Circulating microRNAs are linked to the onset and progression of type 1 diabetes mellitus (T1DM), making them potential biomarkers for the disease. In this study, we employ a multiplatform sequencing approach to analyze circulating microRNAs in an extended cohort of individuals with T1DM from the INNODIA consortium. Our findings reveal that a set of microRNAs located within the T1DM susceptibility chromosomal locus 14q32 distinguishes two subgroups of individuals. To validate our results, we conduct additional analyses on a second cohort of T1DM individuals, confirming the identification of these subgroups, which we have named Cluster A and Cluster B. Remarkably, Cluster B T1DM individuals, who exhibit increased expression of a set of 14q32 miRNAs, show better glycaemic control and display a different blood immunomics profile. Our findings suggest that this set of circulating microRNAs can identify two different T1DM subgroups with distinct blood immunomics at baseline and clinical outcomes during follow-up.

2024-05-03 | GSE265981 | GEO

A set of circulating microRNAs belonging to the 14q32 chromosomic locus identifies two different subgroups of individuals with recent onset Stage 3 type 1 diabetes [first cohort, untargeted]

2024-05-03 | GSE265980 | GEO

A set of circulating microRNAs belonging to the 14q32 chromosomic locus identifies two different subgroups of individuals with recent onset Stage 3 type 1 diabetes [second cohort, untargeted]

Project description:A set of circulating microRNAs belonging to the 14q32 chromosomic locus identifies two different subgroups of individuals with recent onset Stage 3 type 1 diabetes [second cohort, untargeted]

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A set of circulating microRNAs belonging to the 14q32 chromosomic locus identifies two different subgroups of individuals with recent onset Stage 3 type 1 diabetes [first cohort, targeted]

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A set of circulating microRNAs belonging to the 14q32 chromosomic locus identifies two different subgroups of individuals with recent onset Stage 3 type 1 diabetes [first cohort, untargeted]

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Deregulated Expression of the 14q32 miRNA Cluster in Clear Cell Renal Cell Carcinomas

Project description:Clear cell renal cell carcinomas (ccRCC) are characterized by arm-wide chromosomal alterations. Loss at 14q is associated with disease aggressiveness in ccRCC, which responds poorly to chemotherapeutics. The 14q locus contains one of the largest miRNA clusters in the human genome; however, little is known about the contribution of these miRNAs to ccRCC pathogenesis. In this regard, we investigated the expression pattern of selected miRNAs at the 14q32 locus in TCGA kidney tumors and in ccRCC cell lines. We validated that the miRNA cluster is downregulated in ccRCC (and cell lines) as well as in papillary kidney tumors relative to normal kidney tissues and primary renal proximal tubule epithelial (RPTEC) cells. We demonstrated that agents modulating expression of DNMT1 (e.g., 5-Aza-deoxycytidine) could modulate miRNA expression in ccRCC cell lines. Lysophosphatidic acid (LPA, a Lysophospholipid mediator elevated in ccRCC) not only increased labile iron content but also modulated expression of 14q32 miRNAs. Through an overexpression approach targeting a subset of 14q32 miRNAs (specifically at subcluster A: miR-431, miR-432, miR-127, and miR-433) in 769-P cells, we uncovered changes in cellular viability and claudin-1, a tight junction marker. A global proteomic approach was implemented using these miRNA overexpressing cell lines which uncovered ATXN2 as a highly downregulated target, which has a role in chronic kidney disease pathogenesis. Collectively, these findings support a contribution of miRNAs at 14q32 in ccRCC pathogenesis.

2023-05-10 | PXD036428 | Pride

Global Profiling in Vestibular Schwannomas Shows Critical Deregulation of MicroRNAs and Upregulation in those included in Chromosomal Region 14q32

Project description:Background: Vestibular Schwannomas are benign tumors that arise from Schwann cells in the VIII cranial pair and usually present NF2 gene mutations and/or loss of heterozygosity on chromosome 22q. Deregulation has also been found in several genes, such as ERBB2 and NRG1. MicroRNAs are non-coding RNAs approximately 21 to 23 nucleotides in length that regulate mRNAs, usually by degradation at the post-transcriptional level. Methods: We used microarray technology to test the deregulation of miRNAs and other non-coding RNAs present in GeneChip miRNA 1.0 (Affymetrix) over 16 vestibular Schwannomas and 3 control-nerves, validating 10 of them by qRT-PCR. Findings: Our results showed the deregulation of 174 miRNAs, including miR-10b, miR-206, miR-183 and miR-204, and the upregulation of miR-431, miR-221, miR-21 and miR-720, among others. The results also showed an aberrant expression of other non-coding RNAs. We also found a general upregulation of the miRNA cluster located at chromosome 14q32. Conclusion: Our results suggest that several miRNAs are involved in tumor formation and/or maintenance and that global upregulation of the 14q32 chromosomal site may represent a therapeutic target for this neoplasm. 16 Vestibular Schwannomas and 3 control-nerves were analysed

2014-03-24 | E-GEOD-43571 | biostudies-arrayexpress

Small RNA sequencing in cells and exosomes identifies eQTLs and 14q32 as a region of active export

Project description:Exosomes are small extracellular vesicles that carry heterogeneous cargo, including RNA, between cells. Increasing evidence suggests that exosomes are important mediators of intercellular communication and biomarkers of disease. Despite this, the variability of exosomal RNA between individuals has not been well quantified. To assess this variability, we sequenced the small RNA of cells and exosomes from a 17-member family. Across individuals, we show that selective export of miRNAs occurs not only at the level of specific transcripts, but that a cluster of 74 mature miRNAs on chromosome 14q32 is massively exported in exosomes while mostly absent from cells. We also observe more inter-individual variability between exosomal samples than between cellular ones and identify four miRNA expression quantitative trait loci (eQTLs) shared between cells and exosomes. Our findings indicate that genomically co-located miRNAs can be exported together and highlight the variability in exosomal miRNA levels between individuals as relevant for exosome use as diagnostics.

2017-03-08 | GSE74759 | GEO

Global Profiling in Vestibular Schwannomas Shows Critical Deregulation of MicroRNAs and Upregulation in those included in Chromosomal Region 14q32

2014-03-24 | GSE43571 | GEO

Modulation of gene expression after inducing expression of 14q32 miRNAs by CRISPR activation technology in lung adenocarcinoma

Project description:Most lung adenocarcinoma deaths are related to metastases, indicating the necessity of detecting and inhibiting tumor cell dissemination. We have identified that overexpression of miRNAs located on 14q32 was associated with metastasis in lung adenocarcinoma patients. For functional analysis, we utilized CRISPR activation technology to increase levels of miRNAs clustered on 14q32 in a coordinated manner, and the results showed that 14q32 miRNA overexpression promoted tumor cell migratory and invasive properties. Whole transcriptome microarray analysis of the miRNA-overexpressing cells was performed to define the underlying molecular mechanisms. Microarray analysis was used to investigate the gene expression changes underlying the tumor cell migratory and invasive properties induced by 14q32 miRNAs in lung adenocarcinoma.

2018-03-12 | GSE99050 | GEO

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