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Endocrine Abstracts (2015) 37 OC9.1 | DOI: 10.1530/endoabs.37.OC9.1

ECE2015 Oral Communications Adrenal 2 (5 abstracts)

Effects of dexamethasone and adrenocorticotropin on circulating microRNA expression in humans

Ivan Igaz 1 , Gabor Nyiro 2 , Zoltan Nagy 3 , Pal Perge 3 , Miklos Toth 3 , Karoly Racz 2, , Peter Igaz 3 & Attila Patocs 4

1Szent Imre Teaching Hospital, Budapest, Hungary; 2Molecular Medicine Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary; 3Semmelweis University, Budapest, Hungary; 4‘Lendulet‐2013’ Hereditary Endocrine Tumors Research Group, Budapest, Hungary.

Objective: MicroRNAs are short non-protein coding RNA molecules involved in the regulation of numerous homeostatic processes via modulating gene expression. There are some data that the expression of microRNA might be modulated by hormones, but the interaction of hormones and circulating microRNAs of adrenocortical origin is mostly unknown.

Methods: The expression of six selected circulating microRNAs (hsa-miR-27a, hsa-miR-125b-2, hsa-miR-200b, hsa-miR-214, hsa-miR-483-5p, hsa-miR-503) was studied in plasma samples of ten individuals examined by 1 mg dexamethasone suppression test and another ten individuals stimulated by 250 μg tetracosactide (adrenocorticotropin). Total RNA was isolated from plasma samples and microRNA expression has been analysed by Taqman RT-qPCR normalized to cel-miR-39 as reference. The expression of hsa-miR-27a was also studied in vitro in NCI-H295R adrenocortical cell line.

Results: From the six circulating microRNAs selected for the in vivo study based on literature data showing their association to adrenocortical cancer or their responsiveness to hormonal stimuli in animal models, only circulating hsa-miR-27a proved to be significantly modulated in vivo: its expression was up-regulated by dexamethasone whereas it was suppressed by adrenocorticotropin. Expression of secreted hsa-miR-27a was significantly induced in culture supernatants of NCI-H295R cells, as well.

Conclusions: hsa-miR-27a expression is modulated by hormones of the hypothalamic-pituitary-adrenal axis both in vitro and in vivo. Dexamethasone induced secreted hsa-miR-27a both in vitro and circulating hsa-miR-27a in vivo. The expression of circulating hsa-miR-483-5p proposed as diagnostic marker for adrenocortical malignancy was not affected by dexamethasone or tetracosactide administration supporting its usefulness for the evaluation of malignancy of adrenocortical lesions.

Disclosure: Hungarian Scientific Research Grant (OTKA K100295 to Peter Igaz; OTKA PD100648 to Attila Patocs) and Technology Innovation Fund, National Developmental Agency (KTIA-AIK-2012-12-1-0010).

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