Browse
Submit Data
Databases
API
Help

Dataset Information

14 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Estradiol-driven metabolism in transwomen associates with reduced circulating extracellular vesicle microRNA-224/452.

ABSTRACT:

Objective

Sex steroid hormones like estrogens have a key role in the regulation of energy homeostasis and metabolism. In transwomen, gender-affirming hormone therapy like estradiol (in combination with antiandrogenic compounds) could affect metabolism as well. Given that the underlying pathophysiological mechanisms are not fully understood, this study assessed circulating estradiol-driven microRNAs (miRs) in transwomen and their regulation of genes involved in metabolism in mice.

Methods

Following plasma miR-sequencing (seq) in a transwomen discovery (n = 20) and validation cohort (n = 30), we identified miR-224 and miR-452. Subsequent systemic silencing of these miRs in male C57Bl/6 J mice (n = 10) was followed by RNA-seq-based gene expression analysis of brown and white adipose tissue in conjunction with mechanistic studies in cultured adipocytes.

Results

Estradiol in transwomen lowered plasma miR-224 and -452 carried in extracellular vesicles (EVs) while their systemic silencing in mice and cultured adipocytes increased lipogenesis (white adipose) but reduced glucose uptake and mitochondrial respiration (brown adipose). In white and brown adipose tissue, differentially expressed (miR target) genes are associated with lipogenesis (white adipose) and mitochondrial respiration and glucose uptake (brown adipose).

Conclusion

This study identified an estradiol-drive post-transcriptional network that could potentially offer a mechanistic understanding of metabolism following gender-affirming estradiol therapy.

SUBMITTER: Florijn BW

PROVIDER: S-EPMC8436186 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Estrogen-driven control of diabetogenic gene networks is associated with reduced levels of miR-224/452 circulating in extracellular vesicles

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-12-01 | GSE147966 | GEO

Estrogen-driven control of diabetogenic gene networks is associated with reduced levels of miR-224/452 circulating in extracellular vesicles [miRNA-Seq]

Project description:Women with diabetes have a higher prevalence of cardiovascular complications than men, suggesting that sex-steroid hormones like estrogen may impact on female health in diabetes. Here we demonstrate that estrogen suppletion and insulin resistance in male-to-female transgenders coincides with lower plasma levels of miR-224 and miR-452 carried in extracellular vesicles. Systemic silencing of miR-224 and miR-452 in mice triggered a prediabetic phenotype with higher plasma insulin levels, increased white adipose lipogenesis and less glucose uptake and mitochondrial respiration in brown adipose tissue. Consistent with a prediabetic metabolic state, RNA sequencing demonstrated differential expression of genes involved in lipogenesis in white adipose tissue and mitochondrial respiration and glucose uptake in brown adipose tissue. In vitro studies confirmed the estrogen-dependent lowering of miR-224 (brown adipocytes) and miR-452 (white adipocytes) and their impact on adipocyte-specific metabolic processes. Collectively, we identified novel estrogen-driven, post-transcriptional networks that could drive the progression to insulin resistance in transwomen and provide potential anti-diabetic therapeutic targets in women.

2020-12-01 | GSE147965 | GEO

Estrogen-driven control of diabetogenic gene networks is associated with reduced levels of miR-224/452 circulating in extracellular vesicles [RNA-Seq]

2020-12-01 | GSE147872 | GEO

E2F1 induces miR-224/452 expression to drive EMT through TXNIP downregulation.

Project description:Malignant melanoma is highly lethal due to its aggressive invasive properties and metastatic dissemination. The transcription factor E2F1 is crucial for melanoma progression through poorly understood mechanisms. Here, we show that the miR-224/miR-452 cluster is significantly increased in advanced melanoma and invasive/metastatic cell lines that express high levels of E2F1. miR-224/miR-452 expression is directly activated by E2F1 through transactivation of the GABRE gene. Ectopic expression of miR-224/miR-452 in less aggressive cells induces EMT and cytoskeletal rearrangements and enhances migration/invasion. Conversely, miR-224/miR-452 depletion in metastatic cells induces the reversal of EMT, inhibition of motility, loss of the invasive phenotype and an absence of lung metastases in mice. We identify the metastasis suppressor TXNIP as new target of miR-224/miR-452 that induces feedback inhibition of E2F1 and show that miR-224/452-mediated downregulation of TXNIP is essential for E2F1-induced EMT and invasion. The E2F1-miR-224/452-TXNIP axis constitutes a molecular signature that predicts patient survival and may help to set novel therapies.

| S-EPMC4264934 | biostudies-literature

Estrogen-driven control of diabetogenic gene networks is associated with reduced levels of miR-224/452 circulating in extracellular vesicles

Project description:Estrogen-driven control of diabetogenic gene networks is associated with reduced levels of miR-224/452 circulating in extracellular vesicles

| PRJNA622678 | ENA

MiRNAs from the Dlk1-Dio3 locus and miR-224/452 cluster contribute to glioblastoma tumor heterogeneity.

Project description:Glioblastoma is one of the most common and aggressive brain tumors and has seen few improvements in patient outcomes. Inter-tumor heterogeneity between tumors of different patients as well as intra-tumor heterogeneity of cells within the same tumor challenge the development of effective drugs. MiRNAs play an essential role throughout the developing brain and regulate many key genes involved in oncogenesis, yet their role in driving many of the processes underlying tumor heterogeneity remains unclear. In this study, we highlight miRNAs from the Dlk1-Dio3 and miR-224/452 clusters which may be expressed cell autonomously and have expression that is associated with cell state genes in glioblastoma, most prominently in neural progenitor-like and mesenchymal-like states respectively. These findings implicate these miRNA clusters as potential regulators of glioblastoma intra-tumoral heterogeneity and may serve as valuable biomarkers for cell state identification.

| S-EPMC11014907 | biostudies-literature

Increased expression of miR-224-5p in circulating extracellular vesicles of patients with reduced coronary flow reserve.

Project description:BackgroundEndothelial and microvascular dysfunction are pivotal causes of major adverse cardiac events predicted by coronary flow reserve (CFR). Extracellular Vesicles (EVs) have been studied extensively in the pathophysiology of coronary artery disease. However, little is known on the impact of the non-coding RNA content of EVs with respect to CFR.MethodsWe carried out a study among 120 patients divided by high-CFR and low-CFR to profile the miRNA content of circulating EVs.ResultsA multiplex array profiling on circulating EVs revealed mir-224-5p (p-value ≤ 0.000001) as the most differentially expressed miRNA in the Low-CFR group and showed a significantly independent relationship to CFR. Literature survey indicated the origin of the miR from liver cells and not of platelet, leukocyte, smooth muscle or endothelial (EC) origin. A q-PCR panel of the conventional cell type-EVs along with hepatic EVs showed that EVs from liver cells showed higher expression of the miR-224-5p. FACS analysis demonstrated the presence of liver-specific (ASGPR-1+/CD14-) EVs in the plasma of our cohort with the presence of Vanin-1 required to enter the EC barrier. Hepatic EVs with and without the miR-224-5p were introduced to ECs in-vitro, but with no difference in effect on ICAM-1 or eNOS expression. However, hepatic EVs elevated endothelial ICAM-1 levels per se independent of the miR-224-5p.ConclusionThis indicated a role of hepatic EVs identified by the miR-224-5p in endothelial dysfunction in patients with Low CFR.

| S-EPMC9290204 | biostudies-literature

Estrogen-driven control of diabetogenic gene networks is associated with reduced levels of miR-224/452 circulating in extracellular vesicles [RNA-Seq]

Project description:Estrogen-driven control of diabetogenic gene networks is associated with reduced levels of miR-224/452 circulating in extracellular vesicles [RNA-Seq]

| PRJNA622444 | ENA

Estrogen-driven control of diabetogenic gene networks is associated with reduced levels of miR-224/452 circulating in extracellular vesicles [miRNA-Seq]

Project description:Estrogen-driven control of diabetogenic gene networks is associated with reduced levels of miR-224/452 circulating in extracellular vesicles [miRNA-Seq]

| PRJNA622680 | ENA

Circulating Extracellular Vesicle MicroRNA as Diagnostic Biomarkers in Early Colorectal Cancer-A Review.

Project description:Colorectal cancer (CRC) is one of the most common malignancies in the developed world, with global deaths expected to double in the next decade. Disease stage at diagnosis is the single greatest prognostic indicator for long-term survival. Unfortunately, early stage CRC is often asymptomatic and diagnosis frequently occurs at an advanced stage, where long-term survival can be as low as 14%. Circulating microRNAs encapsulated in extracellular vesicles (EVs) have recently come to prominence as novel diagnostic markers for cancer. EV-miRNAs are dysregulated in the circulation of CRC patients compared to healthy controls, and several specific miRNA candidates have been posited as diagnostic markers, including miR-21, miR-23a, miR-1246, and miR-92a. This review outlines the current landscape of EV-miRNAs as potential diagnostic markers for CRC, with a specific focus on those able to detect early stage disease.

| S-EPMC7016718 | biostudies-literature

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