Circulating microRNA Expression in Cushing’s Syndrome

Vetrivel, Sharmilee; Zhang, Ru; Engel, Mareen; Altieri, Barbara; Braun, Leah; Oßwald, Andrea; Bidlingmaier, Martin; Faßnacht, Martin; Beuschlein, Felix; Reincke, Martín; Chen, Alon; Sbiera, Silviu; Riester, Anna

doi:10.3389/fendo.2021.620012

Cited by 19 publications

(11 citation statements)

References 41 publications

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“…Были проведены высокопроизводительное секвенирование образцов сыворотки пациентов, а также валидизация полученных микроРНК методом количественной ПЦР. Выявлено, что miR-182-5p значимо отличалась у пациентов с БИК по сравнению с кортикостеромой надпочечника и группой контроля [37]. В исследовании B. Lu и соавт.…”

Section: обсуждение сопоставление с другими публикациямиunclassified

Differences in plasma miRNA levels in inferior petrosal sinus samples of patients with ACTH-dependent Cushing’s syndrome

Malygina¹,

Belaya²,

Nikitin

et al. 2021

Probl Endokrinol (Mosk)

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BACKGROUND: For the last decades microRNAs (miR) have proven themselves as novel biomarkers for various types of diseases. Identification of specific circulating microRNA panel that differ patient with Cushing’s disease (CD) and ectopic ACTH syndrome (EAS) could improve the diagnostic procedure.AIM: to evaluate the differences in miR levels in plasma samples drained from inferior petrosal sinuses in patients with CD and EAS.MATERIALS AND METHODS: single-center, case-control study: we enrolled 24 patients with ACTH-dependent Cushing’s syndrome (CS) requiring bilateral inferior petrosal sinus sampling (BIPSS). Among them 12 subjects were confirmed as CD (males=2, females=10; median age 46,5 [IR 33,8;53,5]) and 12 as EAS (males=4, females=8, median age 54 [IR 38,75;60,75]). BIPSS was performed through a percutaneous bilateral approach. Once catheters were properly placed, blood samples were withdrawn simultaneously from each petrosal sinus and a peripheral vein. Plasma samples from both sinuses were centrifuged and then stored at -80 C. MiRNA isolation from plasma was carried out by an miRneasy Plasma/Serum Kit (Qiagen, Germany) on the automatic QIAcube station according to the manufacturer protocol. To prevent degradation, we added 1 unit of RiboLock Rnase Inhibitor (Thermo Fisher Scientific, USA) per 1 μL of RNA solution. The concentration of total RNA in the aqueous solution was evaluated on a NanoVue Plus spectrophotometer (GE Healthcare, USA). The libraries were prepared by the QIAseq miRNA Library Kit following the manufacturer standard protocols. MiR expression was then analyzed by sequencing on Illumina NextSeq 500 (Illumina, USA).RESULTS: 108 miRNAs were differently expressed (p <0,05) in inferior petrosal sinus samples of patients with CD vs EAS. We divided these miRNAs into 3 groups based on the significance of the results. The first group consisted of samples with the highest levels of detected miR in both groups. Four miRNAs were included: miR-1203 was downregulated in CD vs EAS — 36.74 (p=0,013), and three other were upregulated in CD vs EAS: miR-383-3p 46.36 (p=0,01), miR-4290 6.84 (p=0,036), miR-6717-5p 4.49 (p=0,031). This miRs will be validated in larger cohorts using RT-qPCR.CONCLUSION: Plasma miR levels differ in inferior petrosal samples taken from patients with CD vs EAS. These miRs need to be validated by different methods and in peripheral plasma samples in order to be used as potentially non-invasive biomarkers to differentiate ACTH-dependent CS.

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Section: обсуждение сопоставление с другими публикациямиunclassified

Differences in plasma miRNA levels in inferior petrosal sinus samples of patients with ACTH-dependent Cushing’s syndrome

Malygina¹,

Belaya²,

Nikitin

et al. 2021

Probl Endokrinol (Mosk)

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“…There are limited studies directly comparing miRNA expression profiles of ACTH-dependent and ACTH-independent CS patients. Consequently, in our previous study, we found differences in expression profiles when comparing circulating miRNAs in CD and CPA patients [ 15 ]. We hypothesized that the presence of ACTH possibly influences the miRNA profile in serum due to the upstream differential expression in the origin tissues.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Adrenal miRNA-Based Dysregulations in Cushing’s Syndrome

Vetrivel

Zhang

Engel

et al. 2022

IJMS

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MiRNAs are important epigenetic players with tissue- and disease-specific effects. In this study, our aim was to investigate the putative differential expression of miRNAs in adrenal tissues from different forms of Cushing’s syndrome (CS). For this, miRNA-based next-generation sequencing was performed in adrenal tissues taken from patients with ACTH-independent cortisol-producing adrenocortical adenomas (CPA), from patients with ACTH-dependent pituitary Cushing’s disease (CD) after bilateral adrenalectomy, and from control subjects. A confirmatory QPCR was also performed in adrenals from patients with other CS subtypes, such as primary bilateral macronodular hyperplasia and ectopic CS. Sequencing revealed significant differences in the miRNA profiles of CD and CPA. QPCR revealed the upregulated expression of miR-1247-5p in CPA and PBMAH (log2 fold change > 2.5, p < 0.05). MiR-379-5p was found to be upregulated in PBMAH and CD (log2 fold change > 1.8, p < 0.05). Analyses of miR-1247-5p and miR-379-5p expression in the adrenals of mice which had been exposed to short-term ACTH stimulation showed no influence on the adrenal miRNA expression profiles. For miRNA-specific target prediction, RNA-seq data from the adrenals of CPA, PBMAH, and control samples were analyzed with different bioinformatic platforms. The analyses revealed that both miR-1247-5p and miR-379-5p target specific genes in the WNT signaling pathway. In conclusion, this study identified distinct adrenal miRNAs as being associated with CS subtypes.

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“…MiRNAs are single-stranded, non-coding RNAs of ~20–24 nucleotides in size ( 13 ). They function as antisense RNAs which regulate their target genes post-transcriptionally, and can influence cellular differentiation, proliferation and apoptosis ( 13 , 14 ). MiRNA expression patterns can be altered in multiple diseases, including cancer ( 15 , 16 ) and Cushing's syndrome in humans ( 14 , 17 , 18 ).…”

Section: Introductionmentioning

confidence: 99%

“…They function as antisense RNAs which regulate their target genes post-transcriptionally, and can influence cellular differentiation, proliferation and apoptosis ( 13 , 14 ). MiRNA expression patterns can be altered in multiple diseases, including cancer ( 15 , 16 ) and Cushing's syndrome in humans ( 14 , 17 , 18 ). MiRNAs that are expressed higher in cancer are regarded as oncomiRs, while miRNAs that are expressed lower in cancer are regarded as tumor suppressor miRNAs ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

Circulating MicroRNAs as Non-invasive Biomarkers for Canine Cushing's Syndrome

et al. 2021

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Canine Cushing's syndrome (hypercortisolism) can be caused by a pituitary tumor (pituitary-dependent hypercortisolism; PDH) or a cortisol-secreting adrenocortical tumor (csACT). For both cases, non-invasive biomarkers that could pre-operatively predict the risk of recurrence after surgery would greatly impact clinical decision making. The aim of this study was to determine whether circulating microRNAs (miRNAs) can be used as diagnostic (presence of PDH or csACT) and/or prognostic (disease recurrence, histological grade) non-invasive biomarkers for canine Cushing's syndrome. After a pilot study with 40 miRNAs in blood samples of healthy dogs (n = 3), dogs with PDH (n = 3) and dogs with a csACT (n = 4), we selected a total of 20 miRNAs for the definitive study. In the definitive study, these 20 miRNAs were analyzed in blood samples of healthy dogs (n = 6), dogs with PDH (n = 19, pre- and post-operative samples) and dogs with a csACT (n = 26, pre-operative samples). In dogs with PDH, six miRNAs (miR-122-5p, miR-126-5p, miR-141-3p, miR-222-3p, miR-375-3p and miR-483-3p) were differentially expressed compared to healthy dogs. Of one miRNA, miR-122-5p, the expression levels did not overlap between healthy dogs and dogs with PDH (p = 2.9x10−4), significantly decreased after hypophysectomy (p = 0.013), and were significantly higher (p = 0.017) in dogs with recurrence (n = 3) than in dogs without recurrence for at least one year after hypophysectomy (n = 7). In dogs with csACTs, two miRNAs (miR-483-3p and miR-223-3p) were differentially expressed compared to healthy dogs. Additionally, miR-141-3p was expressed significantly lower (p = 0.009) in dogs with csACTs that had a histopathological Utrecht score of ≥ 11 compared to those with a score of <11. These results indicate that circulating miRNAs have the potential to be non-invasive biomarkers in dogs with Cushing's syndrome that may contribute to clinical decision making.

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Circulating microRNA Expression in Cushing’s Syndrome

Cited by 19 publications

References 41 publications

Differences in plasma miRNA levels in inferior petrosal sinus samples of patients with ACTH-dependent Cushing’s syndrome

Differences in plasma miRNA levels in inferior petrosal sinus samples of patients with ACTH-dependent Cushing’s syndrome

Characterization of Adrenal miRNA-Based Dysregulations in Cushing’s Syndrome

Circulating MicroRNAs as Non-invasive Biomarkers for Canine Cushing's Syndrome

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