Analysis of Circulating MicroRNAs In Vivo following Administration of Dexamethasone and Adrenocorticotropin

地塞米松和促肾上腺皮质激素给药后体内循环微小RNA的分析

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作者:Ivan Igaz, Gábor Nyírő, Zoltán Nagy, Henriett Butz, Zsolt Nagy, Pál Perge, Peter Sahin, Miklós Tóth, Károly Rácz, Peter Igaz, Attila Patócs

Abstract

Purpose. The interaction of hormones of the pituitary-adrenal axis and adrenal cortex-associated circulating microRNAs is mostly unknown. We have studied the effects of dexamethasone and adrenocorticotropin on the expression of five circulating microRNAs (hsa-miR-27a, hsa-miR-200b, hsa-miR-214, hsa-miR-483-5p, and hsa-miR-503) reported to be related to the adrenal cortex in plasma samples. Methods. Expression of microRNAs was studied in plasma samples of 10 individuals examined by 1 mg dexamethasone suppression test and another 10 individuals stimulated by 250 μg tetracosactide (adrenocorticotropin). Total RNA was isolated and microRNA expression was analyzed by real-time reverse transcription quantitative polymerase chain reaction normalized to cel-miR-39 as reference. Results. Only circulating hsa-miR-27a proved to be significantly modulated in vivo by hormonal treatments: its expression was upregulated by dexamethasone whereas it was suppressed by adrenocorticotropin. Secreted hsa-miR-27a was significantly induced by dexamethasone in vitro in NCI-H295R cells, as well. The expression of hsa-miR-483-5p proposed as diagnostic marker for adrenocortical malignancy was not affected by dexamethasone or tetracosactide administration. Conclusions. hsa-miR-27a expression is modulated by hormones of the hypothalamic-pituitary-adrenal axis both in vitro and in vivo. The biological relevance of hsa-miR-27a modulation by hormones is unclear, but the responsiveness of circulating microRNAs to hormones of the pituitary-adrenal axis is noteworthy.

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