Downregulation of miR-192-5p and miR-204-5p in nonclassic apparent mineralocorticoid excess
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE138556 | GEO | 2020/04/14
REPOSITORIES: GEO
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Project description:BACKGROUND:The "nonclassic" apparent mineralocorticoid excess (NC-AME) has been identified in approximately 7% of general population. This phenotype is characterized by low plasma renin activity (PRA), high serum cortisol (F) to cortisone (E) ratio, low cortisone, high Fractional Excretion of potassium (FEK) and normal-elevated systolic blood pressure (SBP). An early detection and/or identification of novel biomarkers of this phenotype could avoid the progression or future complications leading to arterial hypertension. Isolation of extracellular vesicles, such as exosomes, in specific biofluids support the identification of tissue-specific RNA and miRNA, which may be useful as novel biomarkers. Our aim was to identify miRNAs within urinary exosomes associated to the NC-AME phenotype. METHODS:We perform a cross-sectional study in a primary care cohort of 127 Chilean subjects. We measured BP, serum cortisol, cortisone, aldosterone, PRA. According to the previous reported, a subgroup of subjects was classified as NC-AME (n?=?10). Urinary exosomes were isolated and miRNA cargo was sequenced by Illumina-NextSeq-500. RESULTS:We found that NC-AME subjects had lower cortisone (p?<?0.0001), higher F/E ratio (p?<?0.0001), lower serum potassium (p?=?0.009) and higher FEK 24 h (p?=?0.03) than controls. We found miR-204-5p (fold-change?=?0.115; p 0.001) and miR-192-5p (fold-change?=?0.246; p 0.03) are both significantly downregulated in NC-AME. miR-192-5p expression was correlated with PRA (r?=?0.45; p 0.028) and miR-204-5p expression with SBP (r?=?-?0.48, p 0.027) and F/E ratio (r?=?-?0.48; p 0.026). CONCLUSIONS:These findings could support a potential role of these miRNAs as regulators and novel biomarkers of the NC-AME phenotype.
| S-EPMC6880399 | biostudies-literature
Project description:Downregulation of miR-192-5p and miR-204-5p in nonclassic apparent mineralocorticoid excess
| PRJNA576379 | ENA
Project description: Not available
| S-EPMC7710826 | biostudies-literature
Project description:Apparent Mineralocorticoid Excess Syndrome Natural History Clinical Protocol - RGSDC 5601
| PRJNA189541 | ENA
Project description:Apparent mineralocorticoid excess is an autosomal recessive form of monogenic disease characterized by juvenile resistant low-renin hypertension, marked hypokalemic alkalosis, low aldosterone levels, and high ratios of cortisol to cortisone metabolites. It is caused by defects in the HSD11B2 gene, encoding the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which is primarily involved in the peripheral conversion of cortisol to cortisone. To date, over 50 deleterious HSD11B2 mutations have been identified worldwide. Multiple molecular mechanisms function in the lowering of 11β-HSD2 activity, including damaging protein stability, lowered affinity for the substrate and cofactor, and disrupting the dimer interface. Genetic polymorphism, environmental factors as well as epigenetic modifications may also offer an implicit explanation for the molecular pathogenesis of AME. A precise diagnosis depends on genetic testing, which allows for early and specific management to avoid the morbidity and mortality from target organ damage. In this review, we provide insights into the molecular genetics of classic and non-classic apparent mineralocorticoid excess and aim to offer a comprehensive overview of this monogenic disease.
| S-EPMC9632093 | biostudies-literature
Project description:We have employed whole genome microarray expression profiling as a discovery platform to screen potential target genes of miR-204-5p in colorectal cancer cell HCT116. HCT116 cells were seeded in 6-cm2 tissue culture plates and transfected with the miR-204-5p mimic or negative control (NC) using Lipofectamine 2000 (Invitrogen, USA). After propagation for 48 hours, total RNA was extracted using TRIzol reagent (Invitrogen, USA). Expression profiling was performed using an Agilent human whole genome oligo microarray chip (4M-CM-^W44K) (Agilent, USA) Expression profiling in HCT116 cells was measured at 48 hours after transfection with miR-204-5p or negative control. Experiments were performed using the two samples without repeat experiment.
2014-07-30 | E-GEOD-59897 | biostudies-arrayexpress
Project description:Cystic fibrosis (CF) and apparent mineralocorticoid excess (AME) syndrome are both autosomal recessive disorders that result from mutations of specific identified genes for each condition. CF is caused by defects in the Cystic fibrosis trans membrane conductance regulator (CFTR) gene which encodes for a protein that functions as a chloride channel and regulates the flow of other ions across the apical surface of epithelial cells. AME is due to the deficiency of 11β-hydroxysteroid dehydrogenase type 2 enzyme (11βHSD2), which is responsible for the peripheral inactivation of cortisol to cortisone. Cortisol excess stimulates the mineralocoritoid receptors (MR) resulting in intense sodium retention, hypokalemia and hypertension. We report on a consanguineous Arab family, in which two sibs inherited both CF and AME. Gene testing for AME revealed previously unreported mutation in the 11βHSD2 gene. This report draws attention to the importance of recognizing the possibility of two recessive disorders in the same child in complex consanguineous families. Moreover, it provides a unique opportunity to highlight the implications of the coexistence of two genetic disorders on patient care and genetic counseling of the family.
| S-EPMC4286850 | biostudies-literature
Project description:We have employed whole genome microarray expression profiling as a discovery platform to screen potential target genes of miR-204-5p in colorectal cancer cell HCT116. HCT116 cells were seeded in 6-cm2 tissue culture plates and transfected with the miR-204-5p mimic or negative control (NC) using Lipofectamine 2000 (Invitrogen, USA). After propagation for 48 hours, total RNA was extracted using TRIzol reagent (Invitrogen, USA). Expression profiling was performed using an Agilent human whole genome oligo microarray chip (4×44K) (Agilent, USA)
2014-07-30 | GSE59897 | GEO
Project description:Nonclassic apparent mineralocorticoid excess (NC-AME) is proposed as a novel clinical condition with a mild phenotypic spectrum that ranges from normotension to severe hypertension. This condition is mainly characterized by a high serum cortisol to cortisone ratio (F/E) and concomitant low cortisone (E), however further metabolic changes in NC-AME have not been studied. A cross-sectional study was performed in a primary-care cohort of 396 Chilean subjects, which were classified in two groups: NC-AME (n = 28) and healthy controls (n = 27). A discovery study based in untargeted metabolomics assay in serum samples from both groups was performed by UPLC-Q-TOF/MS. Global metabolomic variations were assayed by principal component analysis and further compared by orthogonal partial least-squares discriminant analysis (OPLS-DA). NC-AME subjects exhibited higher values of blood pressure, fractional excretion of potassium, and lower plasma renin activity and urinary sodium to potassium ratio. Metabolomic analyses showed 36 differentially regulated metabolites between NC-AME and control subjects. A ROC curve analyses identified eight metabolites with high discriminatory capacity between NC-AME and control subjects. Moreover, gamma-L-glutamyl-L-methionine sulfoxide and 5-sulfoxymethylfurfural, exhibited significant association with cortisone, which are potential biomarkers of NC-AME, however further assays should elucidate its biological role in setup and progression of this phenotype.
| S-EPMC8387493 | biostudies-literature
Project description:Melanoma treatment with the BRAF V600E inhibitor vemurafenib provides therapeutic benefits but the common emergence of drug resistance remains a challenge. We generated A375 melanoma cells resistant to vemurafenib with the goal of investigating changes in miRNA expression patterns that might contribute to resistance. Increased expression of miR-204-5p and miR-211-5p occurring in vemurafenib-resistant cells was determined to impact vemurafenib response. Their expression was rapidly affected by vemurafenib treatment through RNA stabilization. Similar effects were elicited by MEK and ERK inhibitors but not AKT or Rac inhibitors. Ectopic expression of both miRNA in drug-naïve human melanoma cells was sufficient to confer vemurafenib resistance and more robust tumor growth in vivo Conversely, silencing their expression in resistant cells inhibited cell growth. Joint overexpression of miR-204-5p and miR-211-5p durably stimulated Ras and MAPK upregulation after vemurafenib exposure. Overall, our findings show how upregulation of miR-204-5p and miR-211-5p following vemurafenib treatment enables the emergence of resistance, with potential implications for mechanism-based strategies to improve vemurafenib responses.Significance: Identification of miRNAs that enable resistance to BRAF inhibitors in melanoma suggests a mechanism-based strategy to limit resistance and improve clinical outcomes. Cancer Res; 78(4); 1017-30. ©2017 AACR.
| S-EPMC5815895 | biostudies-literature