Dataset Information

Circulating microRNA Expression in Cushing's Syndrome.

ABSTRACT:

Context

Cushing's syndrome (CS) is a rare disease of endogenous hypercortisolism associated with high morbidity and mortality. Diagnosis and classification of CS is still challenging.

Objective

Circulating microRNAs (miRNAs) are minimally invasive diagnostic markers. Our aim was to characterize the circulating miRNA profiles of CS patients and to identify distinct profiles between the two major CS subtypes.

Methods

We included three groups of patients from the German Cushing's registry: ACTH-independent CS (Cortisol-Producing-Adenoma; CPA), ACTH-dependent pituitary CS (Cushing's Disease; CD), and patients in whom CS had been ruled out (controls). Profiling of miRNAs was performed by next-generation-sequencing (NGS) in serum samples of 15 CS patients (each before and after curative surgery) and 10 controls. Significant miRNAs were first validated by qPCR in the discovery cohort and then in an independent validation cohort of 20 CS patients and 11 controls.

Results

NGS identified 411 circulating miRNAs. Differential expression of 14 miRNAs were found in the pre- and postoperative groups. qPCR in the discovery cohort validated 5 of the significant miRNAs from the preoperative group analyses. Only, miR-182-5p was found to be significantly upregulated in the CD group of the validation cohort. Comparing all CS samples as a group with the controls did not reveal any significant differences in expression.

Outcome

In conclusion, our study identified miR-182-5p as a possible biomarker for CD, which has to be validated in a prospective cohort. Furthermore, our results suggest that presence or absence of ACTH might be at least as relevant for miRNA expression as hypercortisolism itself.

SUBMITTER: Vetrivel S

PROVIDER: S-EPMC7937959 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Circulating microRNA Expression in Cushing's Syndrome.

Vetrivel Sharmilee S Zhang Ru R Engel Mareen M Altieri Barbara B Braun Leah L Osswald Andrea A Bidlingmaier Martin M Fassnacht Martin M Beuschlein Felix F Reincke Martin M Chen Alon A Sbiera Silviu S Riester Anna A

Frontiers in endocrinology 20210222

<h4>Context</h4>Cushing's syndrome (CS) is a rare disease of endogenous hypercortisolism associated with high morbidity and mortality. Diagnosis and classification of CS is still challenging.<h4>Objective</h4>Circulating microRNAs (miRNAs) are minimally invasive diagnostic markers. Our aim was to characterize the circulating miRNA profiles of CS patients and to identify distinct profiles between the two major CS subtypes.<h4>Methods</h4>We included three groups of patients from the German Cushin ...[more]

PMID: 33692756

Similar Datasets

Project description:PurposeImpairment of skeletal muscle mass and strength affects 40-70% of patients with active Cushing's syndrome (CS). Glucocorticoid excess sustains muscle atrophy and weakness, while muscle-specific microRNAs (myomiRs) level changes were associated with muscle organization and function perturbation. The aim of the current study is to explore changes in circulating myomiRs in CS patients compared to healthy controls and their involvement in IGFI/PI3K/Akt/mTOR pathway regulation in skeletal muscle.MethodsC2C12, mouse myocytes, were exposed to hydrocortisone (HC), and atrophy-related gene expression was investigated by RT-qPCR, WB and IF to assess HC-mediated atrophic signalling. miRNAs were evaluated in HC-treated C2C12 by PCR Arrays. MyomiRs significantly overexpressed in C2C12 were investigated in 37 CS patients and 24 healthy controls serum by RT-qPCR. The anti-anabolic role of circulating miRNAs significantly upregulated in CS patients was explored in C2C12 by investigating the IGFI/PI3K/Akt/mTOR pathway regulation.ResultsHC induced higher expression of atrophy-related genes, miR-133a-3p, miR-122-5p and miR-200b-3p in C2C12 compared to untreated cells. Conversely, the anabolic IGFI/PI3K/Akt/mTOR signalling was reduced and this effect was mediated by miR-133a-3p. In CS patients miR-133a-3p and miR-200b-3p revealed higher circulating levels (p < 0.0001, respectively) compared to controls. ROC curves for miR-133a-3p (AUC 0.823, p < 0.0001) and miR-200b-3p (AUC 0.850, p < 0.0001) demonstrated that both myomiRs represent potential biomarkers to discriminate between CS and healthy subjects. Pearson's correlation analysis revealed that circulating levels of miR-133a-3p are directly correlated with 24 h urinary-free cortisol level (r = 0.468, p = 0.004) in CS patients.ConclusionsHC induces atrophic signals by miR-133a-3p overexpression in mouse myocytes and humans. Circulating miR-133a-3p is promising biomarkers of hypercortisolism.

Dataset Information

Circulating microRNA Expression in Cushing's Syndrome.

Context

Objective

Methods

Results

Outcome

Publications

Circulating microRNA Expression in Cushing's Syndrome.

Similar Datasets

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