Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2021) 75 A17 | DOI: 10.1530/endoabs.75.A17


1LMU Klinikum;; 1Medizinische Klinik und Poliklinik IV, LMU Klinikum, Ludwig-Maximilians-University, Munich, Germany; 2Max Planck Institute of Psychiatry, Munich, Germany; 3Klinik für Endokrinologie, Diabetologie und Klinische Ernährung, Universitätsspital Zürich, Zürich, Switzerland; 4Weizmann Institute of Science, Rehovot, Israel; 5Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, Würzburg, Germany

Introduction: Transcriptional regulation of gene expression by miRNAs is critical for the fine-tuning of adrenal stress response. However, its role in hypercortisolism has not been explored well. The study addresses this gap using adrenal samples of 3 patient groups from the German Cushing’s registry: Cortisol-Producing-Adenoma (CPA), Primary Bilateral Adrenal Hyperplasia (PBMAH) and controls (adrenal samples of patients with pheochromocytoma).

Methods: Next generation sequencing based miRNA profiling and associated target analyses by QPCR were performed. Transcriptomic data of RNA-Seq were analysed and validated by QPCR. For pathway mapping bioinformatic tools (R, String, KEGG, Gprofiler) were used.

Results: miRNA based NGS revealed 23 miRNAs to be differentially expressed between Cushing (PBMAH and CPA) and Controls. Of these, significantly upregulated miRNAs (n=6) were used for validation. Upregulated expression of hsa-miR-139-3p (l2fc>1.4), hsa-miR-1247-5p (l2fc>2.5) and hsa-miR-150-5p (l2fc>1.9) in PBMAH and CPA (vs Controls) could be confirmed by QPCR (P<0.05). Next, the experimentally validated targets of the individual miRNAs were selected from miRWALK and majority of the selected genes were found to be involved in steroid biosynthesis (Alox15, Cyp2b6, Cybrd1). In-vitro and QPCR analyses of the targets are in process. In case of RNA seq, PBMAH was found to have the most dysregulated genes compared to Controls and CPA (n=1248). Pathway mapping using the significantly altered genes in PBMAH gave neuronal synaptic signalling as top hits. Specifically, there was an increased expression (l2fc >5; P<0.05) of dopamine (Drd2) and glutamate receptors (Gria4, Grin2a) in PBMAH. Validation of the pathway analysis is on-going.

Conclusion: This study identifies a miRNA-target gene network in possible steroid biosynthesis dysfunctions in adrenals of patients with Cushing’s syndrome. Additionally, potential changes in neuronal synaptic pathways in PBMAH were identified.

Volume 75

ESE Young Endocrinologists and Scientists (EYES) Annual Meeting

European Society of Endocrinology 

Browse other volumes

Article tools

My recent searches

No recent searches.