Circulating miR-20a-5p as a biomarker associated with cabergoline responsiveness in patients with hyperprolactinemia and pituitary adenomas.

IF 5.3 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Yang Jong Lee, Jae Won Hong, Yongjae Kim, Jisup Kim, Chan Woo Kang, Min-Ho Lee, Ju Hyung Moon, Eui Hyun Kim, Cheol Ryong Ku, Eun Jig Lee
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引用次数: 0

Abstract

Objective: Dopamine agonist (DA) treatment is effective for hyperprolactinemia and reduces tumor size in patients with prolactinoma; however, prolonged DA administration without prolactinoma causes fibrosis around tumor tissues. Therefore, we aimed to identify circulating microRNAs (miRNAs) as potential biomarkers to predict prolactinoma in patients with hyperprolactinemia and pituitary tumors.

Design: Plasma samples were collected from 3 comparison groups: (1) patients clinically diagnosed with prolactinoma vs nonfunctioning pituitary adenoma (NFPA) based on response to cabergoline treatment, (2) patients with surgically confirmed prolactinoma vs NFPA, and (3) patients before and after cabergoline treatment. Candidate miRNAs from the initial nCounter assay were validated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in a larger cohort of 247 patients with hyperprolactinemia and 37 controls.

Methods: The nCounter assay was used for miRNA expression profiling, and the qRT-PCR validated the candidate miRNAs in the plasma and tumor tissue samples. Total RNA sequencing was conducted on pituitary tumor tissues to identify transcriptomic alterations. Furthermore, candidate miRNA target genes and their biological roles were analyzed using prolactinoma cell lines.

Results: Three miRNA candidates (miR-20a-5p, miR-424-5p, and miR-514a-5p) were selected by analyzing 3 sets of expression comparisons between the 2 groups. Furthermore, the relative miR-20a-5p expression significantly increased in prolactinoma compared with that in normal pituitary glands, NFPA, growth hormone-secreting pituitary adenoma, and adrenocorticotropic hormone-secreting pituitary adenoma. In MMQ and GH4 cells, miR-20a-5p inhibition decreased prolactinoma cell proliferation and prolactin secretion.

Conclusions: Circulating miR-20a-5p is a potential biomarker for prolactinoma, which could be associated with responsiveness to DAs.

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来源期刊
European Journal of Endocrinology
European Journal of Endocrinology 医学-内分泌学与代谢
CiteScore
9.80
自引率
3.40%
发文量
354
审稿时长
1 months
期刊介绍: European Journal of Endocrinology is the official journal of the European Society of Endocrinology. Its predecessor journal is Acta Endocrinologica. The journal publishes high-quality original clinical and translational research papers and reviews in paediatric and adult endocrinology, as well as clinical practice guidelines, position statements and debates. Case reports will only be considered if they represent exceptional insights or advances in clinical endocrinology. Topics covered include, but are not limited to, Adrenal and Steroid, Bone and Mineral Metabolism, Hormones and Cancer, Pituitary and Hypothalamus, Thyroid and Reproduction. In the field of Diabetes, Obesity and Metabolism we welcome manuscripts addressing endocrine mechanisms of disease and its complications, management of obesity/diabetes in the context of other endocrine conditions, or aspects of complex disease management. Reports may encompass natural history studies, mechanistic studies, or clinical trials. Equal consideration is given to all manuscripts in English from any country.
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