Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The miR-23-27-24 cluster: an emerging target in NAFLD pathogenesis.

ABSTRACT: The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing globally, being the most widespread form of chronic liver disease in the west. NAFLD includes a variety of disease states, the mildest being non-alcoholic fatty liver that gradually progresses to non-alcoholic steatohepatitis, fibrosis, cirrhosis, and eventually hepatocellular carcinoma. Small non-coding single-stranded microRNAs (miRNAs) regulate gene expression at the miRNA or translational level. Numerous miRNAs have been shown to promote NAFLD pathogenesis and progression through increasing lipid accumulation, oxidative stress, mitochondrial damage, and inflammation. The miR-23-27-24 clusters, composed of miR-23a-27a-24-2 and miR-23b-27b-24-1, have been implicated in various biological processes as well as many diseases. Herein, we review the current knowledge on miR-27, miR-24, and miR-23 in NAFLD pathogenesis and discuss their potential significance in NAFLD diagnosis and therapy.

SUBMITTER: Ru L

PROVIDER: S-EPMC9061717 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

The miR-23-27-24 cluster: an emerging target in NAFLD pathogenesis.

Ru Lin L Wang Xiao-Mei XM Niu Jun-Qi JQ

Acta pharmacologica Sinica 20211210 5

The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing globally, being the most widespread form of chronic liver disease in the west. NAFLD includes a variety of disease states, the mildest being non-alcoholic fatty liver that gradually progresses to non-alcoholic steatohepatitis, fibrosis, cirrhosis, and eventually hepatocellular carcinoma. Small non-coding single-stranded microRNAs (miRNAs) regulate gene expression at the miRNA or translational level. Numerous miRNAs have bee ...[more]

PMID: 34893685

Similar Datasets

An exploration of evolution, maturation, expression and function relationships in mir-23 ∼ 27 ∼ 24 cluster.

Project description:The study aims to explore the potential relationships of evolution, maturation, expression and function between homologous/clustered miRNAs. mir-23 ∼ 27 ∼ 24 gene cluster, including the two gene clusters (mir-23a and mir-23b) and the three miRNA gene families (mir-23, mir-27 and mir-24), was typically selected as an example. These related miRNAs show similar evolutionary patterns and various expression patterns. Most of them show consistent isomiR expression pattern, and the "switching" phenomenon can be found between different abundant isomiR species. These findings suggest that these sequence or location related miRNAs show the similar miRNA processing and maturation processes, and the robust selection of the most dominant isomiR exists in specific tissues. Functional analysis show that these miRNAs show similar distributions of enriched gene categories, suggesting the close functional prelateships via direct or indirect coordinate regulation in biological processes. The study reveals the close evolutionary, expression and functional relationships between related homologous/clustered miRNAs, which will further enrich miRNA studies and understand direct or indirect interactions between miRNAs.

| S-EPMC4144971 | biostudies-literature

The Poly-cistronic miR-23-27-24 Complexes Target Endothelial Cell Junctions: Differential Functional and Molecular Effects of miR-23a and miR-23b.

Project description:The regulation of function of endothelial cell-cell junctions is fundamental in sustaining vascular integrity. The polycistronic microRNA (miR) complexes containing miR-23a-27a-24-2, and 23b-27b-24-1 are predicted to target the majority of major endothelial junctional proteins. We focus on miR-23a and miR-23b, and investigate the functional effects of these miRs on junctions. While miR-23a and 23b only differ by 1 nucleotide (g19) outside the seed region and thus are predicted to have the same targets, they function differently with miR-23a inhibiting permeability and miR-23b inhibiting angiogenesis. Both miRs target the junctional attractive molecule (tight junction protein 2) ZO-2 and the repulsive molecule junctional adhesion molecule C (JAM-C), although the inhibition of JAM-C by miR-23a is more profound than by miR-23b. The difference in potency is attributable to differences at g19 since a mutation of the t17, the g19 binding site of miR-23b in the 3'UTR of JAM-C restores identity. We also show that the pattern of expression of miR-23a and miR-23b and their targets are different. Thus, the paralogues miR-23a and miR-23b can have profoundly different effects on endothelial cell function due at least partially to selective effects on target proteins and differences in expression patterns of the miRs. This work exposes a hitherto unappreciated complexity in therapeutically targeting miRs.

| S-EPMC5023406 | biostudies-literature

miR-23∼27∼24 clusters control effector T cell differentiation and function.

Project description:Coordinated repression of gene expression by evolutionarily conserved microRNA (miRNA) clusters and paralogs ensures that miRNAs efficiently exert their biological impact. Combining both loss- and gain-of-function genetic approaches, we show that the miR-23∼27∼24 clusters regulate multiple aspects of T cell biology, particularly helper T (Th) 2 immunity. Low expression of this miRNA family confers proper effector T cell function at both physiological and pathological settings. Further studies in T cells with exaggerated regulation by individual members of the miR-23∼27∼24 clusters revealed that miR-24 and miR-27 collaboratively limit Th2 responses through targeting IL-4 and GATA3 in both direct and indirect manners. Intriguingly, although overexpression of the entire miR-23 cluster also negatively impacts other Th lineages, enforced expression of miR-24, in contrast to miR-23 and miR-27, actually promotes the differentiation of Th1, Th17, and induced regulatory T cells, implying that under certain conditions, miRNA families can fine tune the biological effects of their regulation by having individual members antagonize rather than cooperate with each other. Together, our results identify a miRNA family with important immunological roles and suggest that tight regulation of miR-23∼27∼24 clusters in T cells is required to maintain optimal effector function and to prevent aberrant immune responses.

| S-EPMC4749926 | biostudies-literature

A MicroRNA Cluster miR-23-24-27 Is Upregulated by Aldosterone in the Distal Kidney Nephron Where it Alters Sodium Transport.

Project description:The epithelial sodium channel (ENaC) is expressed in the epithelial cells of the distal convoluted tubules, connecting tubules, and cortical collecting duct (CCD) in the kidney nephron. Under the regulation of the steroid hormone aldosterone, ENaC is a major determinant of sodium (Na+ ) and water balance. The ability of aldosterone to regulate microRNAs (miRs) in the kidney has recently been realized, but the role of miRs in Na+ regulation has not been well established. Here we demonstrate that expression of a miR cluster mmu-miR-23-24-27, is upregulated in the CCD by aldosterone stimulation both in vitro and in vivo. Increasing the expression of these miRs increased Na+ transport in the absence of aldosterone stimulation. Potential miR targets were evaluated and miR-27a/b was verified to bind to the 3'-untranslated region of intersectin-2, a multi-domain protein expressed in the distal kidney nephron and involved in the regulation of membrane trafficking. Expression of Itsn2 mRNA and protein was decreased after aldosterone stimulation. Depletion of Itsn2 expression, mimicking aldosterone regulation, increased ENaC-mediated Na+ transport, while Itsn2 overexpression reduced ENaC's function. These findings reinforce a role for miRs in aldosterone regulation of Na+ transport, and implicate miR-27 in aldosterone's action via a novel target. J. Cell. Physiol. 232: 1306-1317, 2017. © 2016 Wiley Periodicals, Inc.

| S-EPMC5426511 | biostudies-literature

The miR-23-27-24 clusters drive lipid-associated macrophage proliferation in obese adipose tissue.

Project description:Identifying molecular circuits that control adipose tissue macrophage (ATM) function is necessary to understand how ATMs contribute to tissue homeostasis and obesity-induced insulin resistance. In this study, we find that mice with a myeloid-specific knockout of the miR-23-27-24 clusters of microRNAs (miRNAs) gain less weight on a high-fat diet but exhibit worsened glucose and insulin tolerance. Analysis of ATMs from these mice shows selectively reduced numbers and proliferation of a recently reported subset of lipid-associated CD9+Trem2+ ATMs (lipid-associated macrophages [LAMs]). Leveraging the role of miRNAs to control networks of genes, we use RNA sequencing (RNA-seq), functional screens, and biochemical assays to identify candidate target transcripts that regulate proliferation-associated signaling. We determine that miR-23 directly targets the mRNA of Eif4ebp2, a gene that restricts protein synthesis and proliferation in macrophages. Altogether, our study demonstrates that control of proliferation of a protective subset of LAMs by noncoding RNAs contributes to protection against diet-induced obesity metabolic dysfunction.

| S-EPMC10712211 | biostudies-literature

HIC1 and miR-23~27~24 clusters form a double-negative feedback loop in breast cancer.

Project description:MicroRNAs (miRNAs) have emerged as a major regulator of the initiation and progression of human cancers, including breast cancer. However, the cooperative effects and transcriptional regulation of multiple miRNAs, especially miRNAs that are present in clusters, remain largely undiscovered. Here we showed that all members of the miR-23~27~24 clusters are upregulated and function as oncogenes in breast cancer and simultaneously target HIC1. Furthermore, we found that HIC1 functions as a transcriptional repressor to negatively control the expression of miR-23~27~24 clusters and forms a double-negative (overall positive) feedback loop. This feedback regulatory pathway is important because overexpression of miR-23~27~24 clusters can remarkably accelerate tumor growth, whereas restoration of HIC1 significantly blocks tumor growth in vivo. A mathematical model was created to quantitatively illustrate the regulatory circuit. Our finding highlights the cooperative effects of miRNAs in a cluster and adds another layer of complexity to the miRNA regulatory network. This study may also provide insight into the molecular mechanisms of breast cancer progression.

| S-EPMC5344204 | biostudies-literature

miR-23~27~24 clusters control effector T cell differentiation and function

Project description:Coordinated repression of gene expression by evolutionarily conserved microRNA (miRNA) clusters and paralogs ensures that miRNAs efficiently exert their biological impact. Combining both loss- and gain-of-function genetic approaches, here we show that the miR-23~27~24 clusters regulate multiple aspects of T cell biology, particularly Th2 immunity. Low expression of this miRNA family confers proper effector T cell function at both physiological and pathological settings. Further studies in T cells with exaggerated regulation by individual members of the miR-23~27~24 clusters revealed miR-24 and miR-27 collaboratively limit Th2 responses through targeting IL-4 and GATA3 in both direct and indirect manners. Intriguingly, while overexpression of the entire miR-23 cluster also negatively impacts other Th lineages, enforced expression of miR-24, in contrast to miR-23 and miR-27, actually promotes the differentiation of Th1, Th17 and iTreg cells, implying that under certain conditions, miRNA families can fine tune the biological effects of their regulation by having individual members antagonize rather than cooperate with each other. Together, our results identify a miRNA family with important immunological roles and suggest tight regulation of miR-23~27~24 clusters in T cells is required to maintain optimal effector function and to prevent aberrant immune responses.

2015-12-11 | GSE75909 | GEO

A miR-23~27~24 regulon that controls follicular helper T cell differentiation

Project description:Follicular helper T (Tfh) cells are essential for generating protective humoral immunity. To date, microRNAs (miRNAs) have emerged as important players in regulating Tfh cell biology. Here, we show that loss of miR-23~27~24 clusters in T cells resulted in elevated Tfh cell frequencies upon different immune challenges whereas overexpression of this miRNA family led to reduced Tfh cell responses. Mechanistically, miR-23~27~24 clusters coordinately control Tfh cells through targeting a network of genes that are crucial for Tfh cell biology. Among them, thymocyte selection-associated HMG-box protein (TOX) was identified as a central transcription regulator in Tfh cell development. TOX is highly up-regulated in both mouse and human Tfh cells in a BCL6-dependent manner. In turn, TOX promotes the expression of multiple molecules that play critical roles in Tfh cell differentiation and function. Collectively, our study on miR-23~27~24-mediated control of humoral immunity reveals a TOX-driven regulatory circuit in orchestrating Tfh cell responses.

2019-08-21 | GSE118698 | GEO

miR-23~27~24 clusters control effector T cell differentiation and function

Project description:Coordinated repression of gene expression by evolutionarily conserved microRNA (miRNA) clusters and paralogs ensures that miRNAs efficiently exert their biological impact. Combining both loss- and gain-of-function genetic approaches, here we show that the miR-23~27~24 clusters regulate multiple aspects of T cell biology, particularly Th2 immunity. Low expression of this miRNA family confers proper effector T cell function at both physiological and pathological settings. Further studies in T cells with exaggerated regulation by individual members of the miR-23~27~24 clusters revealed miR-24 and miR-27 collaboratively limit Th2 responses through targeting IL-4 and GATA3 in both direct and indirect manners. Intriguingly, while overexpression of the entire miR-23 cluster also negatively impacts other Th lineages, enforced expression of miR-24, in contrast to miR-23 and miR-27, actually promotes the differentiation of Th1, Th17 and iTreg cells, implying that under certain conditions, miRNA families can fine tune the biological effects of their regulation by having individual members antagonize rather than cooperate with each other. Together, our results identify a miRNA family with important immunological roles and suggest tight regulation of miR-23~27~24 clusters in T cells is required to maintain optimal effector function and to prevent aberrant immune responses. naÃ¯ve T cells isolated from mice with T cell-specific overexpression of the entire miR-23 cluster or individual miR-23 family members as well as from mice with T cell-specific deletion of both miR-23a/b clusters

2015-12-11 | E-GEOD-75909 | biostudies-arrayexpress

The miR-23-27-24 Clusters Drive Lipid-Associated Macrophage Proliferation in Obese Adipose Tissue

Project description:To determine how the miR-23-27-24 miRNA clusters regulate adipose tissue macrophage (ATM) programming in obesity, we placed control mice and mice containing a myeloid-specific deletion of the clusters on high-fat diet for 20weeks. Following dietary intervention, we performed bulk RNA-seq on F4/80 bead-selected ATMs from obese adipose tissue of control and knockout mice.

2023-06-30 | GSE222351 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data