TY  - JOUR
A1  - Vetrivel, Sharmilee
A1  - Zhang, Ru
A1  - Engel, Mareen
A1  - Oßwald, Andrea
A1  - Watts, Deepika
A1  - Chen, Alon
A1  - Wielockx, Ben
A1  - Sbiera, Silviu
A1  - Reincke, Martin
A1  - Riester, Anna
T1  - Characterization of adrenal miRNA-based dysregulations in Cushing's syndrome
JF  - International Journal of Molecular Sciences
N2  - 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.
KW  - cortisol
KW  - ACTH
KW  - miRNA
KW  - Cushing's
KW  - hypercortisolism
KW  - pituitary
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284394
SN  - 1422-0067
VL  - 23
IS  - 14
ER  -