Abstract
Glucocorticoids (GCs) are pleiotropic hormones which regulate innumerable physiological processes. Their comprehensive effects are due to the diversity of signaling mechanism networks. MiRNAs, small, non-coding RNAs contribute to the fine tuning of signaling pathways and reciprocal regulation between GCs and miRNAs has been suggested. Our aim was to investigate the expressional change and potential function of GC mediated miRNAs. The miRNA expression profile was measured in three models: human adrenocortical adenoma vs. normal tissue, steroid-producing H295R cells and in hormonally inactive HeLa cells before and after dexamethasone treatment. The gene expression profile in 82 control and 57 GC-affected samples was evaluated in GC producing and six different GC target tissue types. Tissue-specific target prediction (TSTP) was applied to identify the most relevant miRNA−mRNA interactions. Glucocorticoid treatment resulted in cell type-dependent miRNA expression changes. However, 19.5% of the influenced signaling pathways were common in all three experiments, of which the Wnt-signaling pathway seemed to be the most affected. Transcriptome data and TSTP showed similar results, as the Wnt pathway was significantly altered in both the GC-producing adrenal gland and all investigated GC target tissue types. In different cell types, different miRNAs led to the regulation of similar pathways. Wnt signaling may be one of the most important signaling pathways affected by hypercortisolism. It is, at least in part, regulated by miRNAs that mediate the glucocorticoid effect. Our findings on GC producing and GC target tissues suggest that the alteration of Wnt signaling (together with other pathways) may be responsible for the leading symptoms observed in Cushing’s syndrome.
Highlights
Glucocorticoids (GCs) are steroid hormones which regulate the various metabolic and homeostatic processes essential for life: inflammatory and immune reactions, metabolic control, fertility and reproduction, cognitive function and development
The expression of 265 individual miRNAs were measured. Of these 265 miRNAs, in adrenal adenoma tissues five miRNAs showed significantly altered expression compared to normal adrenal tissue, in H295R and HeLa cells expression of six and eight miRNAs exhibited statistically significant change, respectively, as detailed below
We presented the hypothesis that the expression profile of both human bone tissue biopsies from Cushing’s syndrome (CS) patients and patient-derived primary osteoblast cell lines treated by dexamethasone indicated that the Wnt pathway was significantly influenced by miRNAs
Summary
Glucocorticoids (GCs) are steroid hormones which regulate the various metabolic and homeostatic processes essential for life: inflammatory and immune reactions, metabolic control, fertility and reproduction, cognitive function and development. Their role is vital for the physiological function of many organs. GCs are essential in the treatment of chronic inflammatory diseases, after organ transplantations and in the field of oncohematology, but the harmful effects accompanying hypercortisolic periods throughout prolonged GC administration represent a serious risk for many pathological conditions. Diverse signaling mechanisms admit glucocorticoids to control the physiological processes at the level of different organs and tissues, but it is difficult to define the “main” signaling pathways which are responsible for these processes. The most studied pathways related to GC signaling are: the GH/IGF-1 axis, TGFβ-SMAD signaling, PI3/Akt signaling, MAPK signaling, Wnt-signaling, BMP signaling and NF-κB signaling [5,6,7,8,9,10,11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
