Ontology highlight
ABSTRACT:
PROVIDER: PRJNA992019 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25161963.fastq.gz | Fastqsanger.gz | |||
| SRR25161964.fastq.gz | Fastqsanger.gz | |||
| SRR25161965.fastq.gz | Fastqsanger.gz |
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Project description:Background/ Aim: Diabetes has substantive co-occurrence with disorders of gut-brain interactions (DGBIs). The pathophysiological and molecular mechanisms linking diabetes and DGBIs are unclear. miRNAs are key regulators of diabetes and gut dysmotility. We investigated whether impaired gut barrier function regulated by a key miRNA, miR-10b-5p, links diabetes and gut dysmotility. Methods: We created a new mouse line using the Mb3Cas12a/Mb3Cpf1 endonuclease to knock out mir-10b globally. Loss of function studies were conducted to characterize diabetes, gut dysmotility, and gut barrier dysfunction phenotypes in these mice. Gain of function studies were conducted by injecting these mice with a miR-10b-5p mimic. Further, we performed miRNA-sequencing analysis from colonic mucosa from mir-10b KO, WT, and miR-10b-5p mimic injected mice to confirm 1) deficiency of miR-10b-5p in KO mice, and 2) restoration of miR-10b-5p expression after the mimic injection. Results: Congenital loss of mir-10b in mice led to the development of hyperglycemia, gut dysmotility, and gut barrier dysfunction. We found increased gut permeability and reduced expression of the tight junction protein Zonula occludens-1 (ZO-1), in the colon of mir-10b KO mice. We further confirmed that patients with diabetes or IBS-C, a known DGBI that is linked to leaky gut, had significantly reduced miR-10b-5p expression. Injection of a miR-10b-5p mimic in mir-10b KO mice rescued these molecular alterations and phenotypes. Conclusion: Our study uncovered a potential pathophysiologic mechanism of gut barrier dysfunction that links both the diabetes and gut dysmotility phenotypes in mice lacking miR-10b-5p. Treatment with a miR-10b-5p mimic reversed the leaky gut, diabetic, and gut dysmotility phenotypes, highlighting the translational potential of miR-10b-5p mimic.
2023-07-13 | GSE236981 | GEO
Project description:The corneal epithelium is maintained by limbal epithelial stem cells (LESCs) and is largely responsible for corneal optical transparency and protection by continuously renewing population of corneal epithelial cells. Diabetes mellitus (DM) affects all structures of the eye including the cornea, which can result in delayed wound healing and potential vision loss. MicroRNAs (miRNAs) are short non-coding oligonucleotides that regulate various cellular functions, including oxidative stress response, by repressing protein translation. MiR-10b-5p was previously identified to be upregulated in diabetic vs. non-diabetic limbal cells, and our purpose was to understand the role of miR-10b-5p in human limbal epithelial cells in healthy and diabetic conditions. Through integrated transcriptomic and proteomic analyses, we identified GCLM and LANCL1 as key miR-10b-5p targets, revealing its profound impact on glutathione metabolism, sulfur compound biosynthesis processes, and antioxidant defenses. Our findings suggest that overexpression of miR-10b disrupts redox balance, which potentially leads to heightened oxidative stress and increased cellular vulnerability in diabetic corneas. Understanding miR-10b function in corneal epithelial cells may pave the way for novel therapeutic strategies to mitigate oxidative stress and normalize corneal health in diabetic patients.
2025-03-14 | MSV000097328 | MassIVE
Project description:The corneal epithelium is maintained by limbal epithelial stem cells (LESCs) and are largely responsible for corneal optical transparency and protection by continuous population of corneal epithelial cells. Diabetes mellitus (DM) has been shown to affect all structures of the eye including the cornea which can result in delayed wound healing and potential vision loss. MicroRNAs (miRNAs) are short non-coding oligonucleotides that regulate various cellular functions, including oxidative stress response, by repressing translation. miR-10b-5p was previously identified to be upregulated in diabetic vs. non-diabetic limbal cells and our purpose was to understand the role of miR-10b-5p in human limbal epithelial cells in normal and pathological conditions such as diabetes mellitus. It was hypothesized that miR-10b-5p influences corneal epithelial homeostasis by modulating antioxidant defenses and wound healing processes. Through integrated transcriptomic and proteomic analyses, we identified GCLM and LANCL1 as key miR-10b-5p targets, revealing its profound impact on glutathione metabolism, sulfur compound biosynthesis processes, and antioxidant defenses. Our finding suggests that miR-10b suppression disrupts redox balance which potentially leads to heightened oxidative stress, impaired wound healing and increased cellular vulnerability in diabetic corneas. Further research into miR-10b inhibitors or gene modulation strategies may pave the way for novel treatments aimed at mitigating oxidative stress-related corneal dysfunction, particularly in diabetes-induced ocular diseases.
2025-07-01 | GSE292721 | GEO
Project description:BACKGROUND MicroRNAs (miRNAs) are small non-coding RNAs that recognize sites of complementarity of target messenger RNAs, resulting in transcriptional regulation and translational repression of target genes. In Huntington’s disease (HD), a neurodegenerative disease caused by a trinucleotide repeat expansion, miRNA dyregulation has been reported, which may impact gene expression and modify the progression and severity of HD. METHODS: We performed next-generation miRNA sequence analysis in prefrontal cortex (Brodmann Area 9) from 26 HD, 2 asymptomatic HD, and 36 control brains. Neuropathological information was available for all HD brains, including age at disease onset, CAG-repeat size, Vonsattel grade, and Hadzi-Vonsattel striatal and cortical scores, a continuous measure of the extent of neurodegeneration. Linear models were performed to examine the relationship of miRNA expression to these clinical features, and messenger RNA targets of associated miRNAs were tested for gene ontology term enrichment. RESULTS: We identified 75 miRNAs differentially expressed in HD brain (FDR q-value <0.05). Among the HD brains, nine miRNAs were significantly associated with Vonsattel grade of neuropathological involvement and three of these, miR-10b-5p, miR-10b-3p, and miR-302a-3p, significantly related to the Hadzi-Vonsattel striatal score (a continuous measure of striatal involvement) after adjustment for CAG length. Five miRNAs (miR-10b-5p, miR-196a-5p, miR-196b-5p, miR-10b-3p, and miR-106a-5p) were identified as having a significant relationship to CAG length-adjusted age of onset including miR-10b-5p, the mostly strongly over-expressed miRNA in HD cases. Although prefrontal cortex was the source of tissue profiled in these studies, the relationship of miR-10b-5p expression to striatal involvement in the disease was independent of cortical involvement. Correlation of miRNAs to the clinical features clustered by direction of effect and the gene targets of the observed miRNAs showed association to processes relating to nervous system development and transcriptional regulation. CONCLUSIONS: These results demonstrate that miRNA expression in cortical BA9 provides insight into striatal involvement and support a role for these miRNAs, particularly miR-10b-5p, in HD pathogenicity. The miRNAs identified in our studies of postmortem brain tissue may be detectable in peripheral fluids and thus warrant consideration as accessible biomarkers for disease stage, rate of progression, and other important clinical characteristics of HD. 26 Huntington's disease, 2 asymptomatic HD gene positive and 49 neurologically normal control prefrontal cortex samples
2015-03-12 | E-GEOD-64977 | biostudies-arrayexpress
Project description:Multisystem smooth muscle dysfunction syndrome (MSMDS) is a smooth muscle myopathy with major dysfunction in multiple organ systems. Described cases have been exclusively associated with recurrent missense variants at amino acid position 179 in the ACTA2 gene. We describe a patient with multiple major manifestations of MSMDS including steno-occlusive cerebrovascular arteriopathy, prune belly syndrome, gastrointestinal dysmotility, bladder dysfunction, and pupillary hyporeactivity without variation in ACTA2. Whole genome sequencing revealed a single nucleotide variant contained within the seed sequence of MIR145, which encodes the smooth muscle associated microRNA; hsa-miR-145-5p. RNA expression analysis on patient-derived fibroblasts was consistent with actin cytoskeletal dysfunction, and mutant miR-145-5p was unable to mediate cytoskeletal modulation of smooth muscle cells. MSMDS can be caused by a loss-of-function mutation in the smooth muscle differentiation factor, miR-145-5p, the first described non-coding genetic vasculopathy.
2023-12-14 | GSE220038 | GEO
Project description:BACKGROUND MicroRNAs (miRNAs) are small non-coding RNAs that recognize sites of complementarity of target messenger RNAs, resulting in transcriptional regulation and translational repression of target genes. In Huntington’s disease (HD), a neurodegenerative disease caused by a trinucleotide repeat expansion, miRNA dyregulation has been reported, which may impact gene expression and modify the progression and severity of HD. METHODS: We performed next-generation miRNA sequence analysis in prefrontal cortex (Brodmann Area 9) from 26 HD, 2 asymptomatic HD, and 36 control brains. Neuropathological information was available for all HD brains, including age at disease onset, CAG-repeat size, Vonsattel grade, and Hadzi-Vonsattel striatal and cortical scores, a continuous measure of the extent of neurodegeneration. Linear models were performed to examine the relationship of miRNA expression to these clinical features, and messenger RNA targets of associated miRNAs were tested for gene ontology term enrichment. RESULTS: We identified 75 miRNAs differentially expressed in HD brain (FDR q-value <0.05). Among the HD brains, nine miRNAs were significantly associated with Vonsattel grade of neuropathological involvement and three of these, miR-10b-5p, miR-10b-3p, and miR-302a-3p, significantly related to the Hadzi-Vonsattel striatal score (a continuous measure of striatal involvement) after adjustment for CAG length. Five miRNAs (miR-10b-5p, miR-196a-5p, miR-196b-5p, miR-10b-3p, and miR-106a-5p) were identified as having a significant relationship to CAG length-adjusted age of onset including miR-10b-5p, the mostly strongly over-expressed miRNA in HD cases. Although prefrontal cortex was the source of tissue profiled in these studies, the relationship of miR-10b-5p expression to striatal involvement in the disease was independent of cortical involvement. Correlation of miRNAs to the clinical features clustered by direction of effect and the gene targets of the observed miRNAs showed association to processes relating to nervous system development and transcriptional regulation. CONCLUSIONS: These results demonstrate that miRNA expression in cortical BA9 provides insight into striatal involvement and support a role for these miRNAs, particularly miR-10b-5p, in HD pathogenicity. The miRNAs identified in our studies of postmortem brain tissue may be detectable in peripheral fluids and thus warrant consideration as accessible biomarkers for disease stage, rate of progression, and other important clinical characteristics of HD.
2015-03-12 | GSE64977 | GEO
Project description:To investigate the functions of miR-10b-5p in uterine leiomyosarcoma, transcriptome analysis was performed.
2022-06-30 | GSE201542 | GEO
Project description:White adipose tissue (WAT) dysfunction along with an aberrant expression of miRNAs are strongly associated with the risk of developing type 2 diabetes (T2D) with limited evidence linking early changes in the WAT-derived miRNAs and T2D. The present study aims to identify early miRNome changes prognostic for T2D in mice and humans. Gonadal (g) WAT of diabetes-resistant and -prone mice were subjected to multi-omics analyses (transcriptome, miRNome, methylome, proteome). Metabolic phenotypes linked with T2D were correlated with adipose tissue miRNA expression and DNA methylation from 14 monozygotic twin pairs discordant for T2D. Plasma miRNA levels from females at high risk of developing T2D (TÜF study) were included. Adipose tissue of the diabetes-susceptible mice was less insulin sensitive with 150 differentially expressed miRNAs compared to diabetes-resistant mice. Integrative analysis of miRNome-transcriptome-proteome identified 61 proteins involved in actin cytoskeleton, amino acid and sphingolipid metabolism. More than 20 miRNAs are located in the imprinted region Dlk1-Gtl2 and miR-335 in Mest and regulated by DNA methylation. Imprinted miRNAs also exhibited similar alteration in monozygotic twin pairs discordant for T2D with miR-335 expression altered only in females. Moreover, plasma levels of miR-335-5p were negatively correlated with fasting blood glucose in female individuals at high risk of developing T2D. Early alterations of WAT-derived miRNAs such as miR-335-5p could contribute to systemic metabolic changes associated with the risk of developing T2D.
2025-12-15 | PXD057291 | Pride
Project description:Multisystemic Smooth Muscle Dysfunction Syndrome (MSMDS) is a rare disorder caused by ACTA2 mutations, including the R179H variant, which disrupts actin polymerization and smooth muscle contractility. While cardiovascular complications dominate its clinical presentation, gastrointestinal (GI) dysfunction significantly impacts quality of life. To investigate the structural, functional, and cellular basis of gut dysmotility in MSMDS, we studied the ACTA2 R179H mouse model and reviewed clinical data from 24 MSMDS patients. Patients exhibited severe gut dysmotility, with 75% requiring medication for chronic constipation. ACTA2 mutant mice displayed cecal and colonic dilatation, reduced intestinal length, and disrupted colonic migrating motor complexes (CMMCs). Delayed whole-gut transit and impaired contractile responses to electrical and pharmacological stimulation were observed. Transcriptomic analysis revealed significant actin cytoskeleton-related gene changes in smooth muscle cells, and immune profiling identified increased lymphocytic infiltration. Despite functional abnormalities, enteric neuronal populations remained unchanged. These findings establish ACTA2 mice as a robust model for studying GI pathology in MSMDS, elucidating the role of smooth muscle dysfunction in gut dysmotility. This model provides a foundation for developing targeted therapies aimed at restoring intestinal motility by directly addressing actin cytoskeletal disruptions in smooth muscle cells.
2025-10-15 | GSE305376 | GEO
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