Circulating miRNA Expression Profiling in Primary Aldosteronism

Decmann, Ábel; Nyírő, G; Darvasi, Ottó; Turai, Péter István; Bancos, Irina; Kaur, Ravinder; Pezzani, Raffaele; Iacobone, Maurizio; Kraljević, Ivana; Kaštelan, Darko; Parasiliti-Caprino, Mirko; Maccario, Mauro; Nirschl, Nina; Heinrich, Daniel A.; Reincke, Martín; Patócs, Attila; Igaz, Péter

doi:10.3389/fendo.2019.00739

Cited by 22 publications

(22 citation statements)

References 39 publications

(44 reference statements)

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“…While only miRNA-146b and miRNA-96-5p were found to be significantly altered between CPA and controls of the discovery cohort, similar differential expression was not observed in the CPA of the validation cohort. The discrepancy might be explained by possible heterogeneity in CPA samples, speculated from previous adenoma studies ( 34 ). Decmann et al recently reported heterogeneity associated with complex underlying pathology to be the possible reason for the observed discordance between NGS and qPCR of adenoma samples.…”

Section: Discussionmentioning

confidence: 84%

“…Therefore, we hypothesized that a potential miRNA based diagnostic should aid in the diagnosis of CS or its subtypes as circulating miRNAs have proven their potential as minimal invasive biomarkers in other diseases ( 33 ). Few studies have investigated circulating miRNA profiles in CS, and appropriate controls matched for sex, BMI and comorbidities were missing ( 17 , 34 ). Therefore, in our study we included clinically relevant control samples to identify a unique circulating miRNA signature associated with CS.…”

Section: Discussionmentioning

confidence: 99%

“…This difference could be possibly explained by the high sensitivity observed with qPCR in comparison to the high throughput genomic profiling technologies including NGS and microarray ( 38 ). Concurrently, studies with a wholesome approach to circulating miRNAs, namely through microarray and NGS, are often not able to validate their sequencing and array results ( 25 , 34 ). miR-182-5p along with miR-96-5p and miR-183-5p, were also found to be deregulated in CPA and CD samples compared to the controls ( Figures 1B, C ).…”

Section: Discussionmentioning

confidence: 99%

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Circulating microRNA Expression in Cushing’s Syndrome

Vetrivel¹,

Zhang²,

Engel

et al. 2021

Front. Endocrinol.

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ContextCushing’s syndrome (CS) is a rare disease of endogenous hypercortisolism associated with high morbidity and mortality. Diagnosis and classification of CS is still challenging.ObjectiveCirculating 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.MethodsWe 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.ResultsNGS 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.OutcomeIn 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.

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Circulating microRNA Expression in Cushing’s Syndrome

Vetrivel¹,

Zhang²,

Engel

et al. 2021

Front. Endocrinol.

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“…Entire intracellular mechanisms of aldosterone production are still complex. In addition, recent basic studies suggested that mRNA translation and translation via miRNA also participate aldosterone regulation in APA [19,[45][46][47], however these have not been fully elucidated. Significant more work including basic studies on the regulation of aldosterone biosynthesis will be necessary for the development of medical therapies for primary aldosteronism and aldosterone-producing adenomas.…”

Section: Discussionmentioning

confidence: 99%

The landscape of molecular mechanism for aldosterone production in aldosterone-producing adenoma

Oki

Gómez-Sánchez

2020

Endocr J

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Primary aldosteronism is the most common form of secondary hypertension with a prevalence of 5-10% in hypertensive patients. Aldosterone-producing adenoma (APA) is a subtype of primary aldosteronism, and somatic mutations in KCNJ5, ATP1A1, ATP2B3, CACNA1D, CLCN2, or CTNNB1 were identified and recognized to drive aldosterone production and/or contribute to tumorigenesis in APA. Mutations of KCNJ5, ATP1A1, ATP2B3, CACNA1D, and CLCN2 are known to activate calcium signaling, and its activation potentiate CYP11B2 (aldosterone synthesis) transcription in adrenal cells. Transcriptome analyses combined with bioinformatics using APA samples were conductive for each gene mutation mediated pivotal pathway, gene ontology, and clustering. Several important intracellular molecules in increase aldosterone production were detected by transcriptome analysis, and additional functional analyses demonstrated intracellular molecular mechanisms of aldosterone production which focused on calcium signal, CYP11B2 transcription and translation. Furthermore, DNA methylation analysis revealed that promoter region of CYP11B2 was entirely hypomethylated, but that of other steroidogenic enzymes were not in APA. Integration of transcriptome and DNA methylome analysis clarified some DNA methylation associated gene expression, and the transcripts have a role for aldosterone production. In this article, we reviewed the intracellular molecular mechanisms of aldosterone production in APA, and discussed future challenges for basic studies leading to clinical practice.

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“…Our research group has evaluated the utility of miRNA biomarkers in the differentiation of APA and BAH [81]. Altogether 123 preoperative plasma samples were processed.…”

Section: Circulating Mirnas As Biomarkers In Primary Aldosteronismmentioning

confidence: 99%

MicroRNAs and Adrenocortical Tumors: Where do we Stand on Primary Aldosteronism?

et al. 2020

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MicroRNAs, the endogenous mediators of RNA interference, interact with the renin-angiotensin-aldosterone system, regulate aldosterone secretion and aldosterone effects. Some novel data show that the expression of some microRNAs is altered in primary aldosteronism, and some of these appear to have pathogenic relevance, as well. Differences in the circulating microRNA expression profiles between the two major forms of primary aldosteronism, unilateral aldosterone-producing adenoma and bilateral adrenal hyperplasia have also been shown. Here, we present a brief synopsis of these findings focusing on the potential relevance of microRNA in primary aldosteronism.

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Circulating miRNA Expression Profiling in Primary Aldosteronism

Cited by 22 publications

References 39 publications

Circulating microRNA Expression in Cushing’s Syndrome

Circulating microRNA Expression in Cushing’s Syndrome

The landscape of molecular mechanism for aldosterone production in aldosterone-producing adenoma

MicroRNAs and Adrenocortical Tumors: Where do we Stand on Primary Aldosteronism?

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