Dataset Information

MiR-29a-3p coordinates the ECM-integrin-adaptor protein axis to regulate focal adhesion in allergic rhinitis [RNA-Seq]

ABSTRACT: MiR-29a-3p plays a crucial role in regulating cell-cell junctions in the nasal mucosa epithelial cells of individuals with allergic rhinitis (AR). However, the impact of miR-29a-3p on focal adhesion (FA) homeostasis or cell-extracellular matrix (ECM) adhesion remains uncertain. This study demonstrates that miR-29a-3p can regulate the expression of LAMC1 and ITGA6, showing a potential correlation with AR pathogenesis in humans. Furthermore, the targeted inhibitory relationship between miR-29a-3p and both LAMC1 and ITGA6 was confirmed through dual-luciferase reporter assays. Analysis of miRNA-seq and mRNA-seq datasets established a differential expression (DE) profile for AR-associated genes, revealing 278 DE-miRNAs and 11,352 DE-mRNAs. Based on this data, we assert that miR-29s are a remarkable example of a single microRNA family exhibiting a consistent upregulation trend in AR. The KEGG analysis showed that AR is significantly associated with FA and ECM-receptor interaction. By integrating online databases for miRNA-target prediction with mRNA-seq data, we identified crucial genes involved in FA (e.g., ITGA6) and cell-ECM adhesion (e.g., LAMC1) as potential targets of miR-29s. Consequently, the role of the entire miRNA transcriptome can be virtually encompassed by miR-29s. In vivo evidence from AR mouse models further supported the role of miR-29a-3p in repressing these proteins' expression. Our findings provide a comprehensive understanding of the significant differential expression of miRNA/mRNA genes in AR, with a specific focus on miR-29a-3p. This particular miRNA appears to hinder the process of FA and cell-ECM adhesion by targeting the ECM-integrins-adaptor protein axis, potentially contributing to the pathogenesis of AR.

ORGANISM(S): Mus musculus

PROVIDER: GSE247293 | GEO | 2024/10/01

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:To investigate the potential role of miRNAs in disease mechanisms, we conducted a thorough analysis by comparing the entire miRNome of 18 vEDS dermal fibroblasts to those of 18 control cells. To improve statistical reliability, we sequenced each sample from both groups as biological replicates. By applying a log2 fold change threshold of greater than 1 or less than -1, and an adjusted p-value of less than 0.05, we identified 137 DE-miRNAs in patient vs. control fibroblasts. Among these, 71 miRNAs exhibited decreased expression, while 66 miRNAs were upregulated. To explore the functional relationship between DE-miRNAs and the altered gene expression profile of vEDS cells, we conducted an extensive review of the literature and consulted several bioinformatics databases. Our search involved utilizing data from four miRNA-target prediction databases (microT-CDS, Targetscan, miRTarBase, and miRwalk) in addition to relevant literature sources providing information on the functional roles of these miRNAs. We thus focused our research on a specific subset of DE-miRNAs, known as miR-15b-5p, miR-16-5p, miR-21-3p, miR-24-3p, miR-29a-3p, miR-29b-3p, miR-138-5p, miR-145-5p, and miR-195-5p, which may play a biological role in dysregulated molecular mechanisms underlying disease pathogenesis. Our initial emphasis was on miR-29a-3p and miR-29b-3p due to their involvement in regulating critical cellular processes such as ECM remodeling into the vascular network, autophagy, cell proliferation, and apoptosis. To study how miR-29a-3p and miR-29b-3p contribute to the dysregulated cellular processes observed in patient cells, we performed GO and pathway enrichment analyses on their predicted target DEGs. GO analysis revealed that both these miRNAs may disturb fundamental biological functions, such as regulation of transcription by RNA polymerase II, negative gene expression regulation, miRNA-mediated gene silencing, translation regulation, heterochromatin organization, and ECM organization. This comphrensive transcriptome analysis of a large cohort of dermal fibroblasts from patients with vEDS reveals deregulated biological functions potentially involved in the disease pathogenesis. Taken together, the abnormal expression of several miRNAs suggests the presence of epigenetic control in vEDS cells, which could influence the transcriptional regulation of numerous target DEGs and related biological processes, potentially influencing disease mechanisms. This work was supported by Fondazione Telethon and the “Associazione con Giacomo contro vEDS”, (Grant number: GSA21F001, Seed Grant Fall 2021 vEDS) to Nicola Chiarelli.

Project description:Background: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic disorder, characterized by cardiomyocyte hypertrophy, cardiomyocyte disarray and fibrosis, which has a prevalence of ~1:200-500 and predisposes individuals to sudden death and heart failure. The mechanisms through which diverse HCM-causing mutations cause cardiac dysfunction remain mostly unknown and their identification may reveal new therapeutic avenues. MicroRNAs have emerged as critical regulators of gene expression and disease phenotype in various pathologies. We explored whether miRNAs could play a role in HCM pathogenesis and offer potential therapeutic targets. Methods and Results: Using high-throughput miRNA expression profiling and qPCR analysis in two distinct mouse models of HCM, we found that miR-199a-3p expression levels are upregulated in mutant mice compared to age- and treatment-matched wild-type mice. We also found that miR-199a-3p expression is enriched in cardiac non-myocytes compared to cardiomyocytes. When we expressed miR-199a-3p mimic in cultured primary cardiac non-myocytes and analyzed the conditioned media by proteomics, we found that several ECM proteins (e.g., TSP2, FBLN3, COL11A1, LYOX) were differentially expressed. We confirmed our proteomics findings by qPCR analysis of selected mRNAs and demonstrated that miR-199a-3p mimic expression in cardiac non-myocytes drives upregulation of ECM genes including Tsp2, Fbln3, Pcoc1, Col1a1 and Col3a1. To examine the role of miR-199a-3p in vivo, we inhibited its function using lock-nucleic acid (LNA)-based inhibitors (antimiR-199a-3p) in an HCM mouse model. Our results revealed that progression of cardiac fibrosis is attenuated when miR-199a-3p function is inhibited in mild-to-moderate HCM. Finally, guided by computational target prediction algorithms, we identified mRNAs Cd151 and Itga3 as direct targets of miR-199a-3p and have shown that miR-199a-3p mimic expression negatively regulates AKT activation in cardiac non-myocytes. Conclusions: Altogether, our results suggest that miR-199a-3p may contribute to cardiac fibrosis in HCM through its actions in cardiac non-myocytes. Thus, inhibition of miR-199a-3p in mild-to-moderate HCM may offer therapeutic benefit in combination with complementary approaches that target the primary defect in cardiac myocytes.

Dataset Information

MiR-29a-3p coordinates the ECM-integrin-adaptor protein axis to regulate focal adhesion in allergic rhinitis [RNA-Seq]

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets