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

European Journal of Endocrinology Pub Date : 2025-03-27 DOI:10.1093/ejendo/lvaf025

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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循环miR-20a-5p作为高催乳素血症和垂体腺瘤患者卡麦角林反应性相关的生物标志物

目的：多巴胺激动剂（DA）治疗高催乳素血症有效，可减小催乳素瘤患者的肿瘤大小；然而，没有泌乳素瘤的长期服用DA会导致肿瘤组织周围纤维化。因此，我们旨在鉴定循环microRNAs （miRNAs）作为预测高催乳素血症和垂体肿瘤患者催乳素瘤的潜在生物标志物。设计：收集3组血浆样本：(1)根据对卡麦角林治疗的反应临床诊断为泌乳素瘤与无功能垂体腺瘤（NFPA）的患者，(2)手术确诊为泌乳素瘤与NFPA的患者，(3)卡麦角林治疗前后的患者。在247名高泌乳素血症患者和37名对照组中，使用定量逆转录聚合酶链反应（qRT-PCR）验证了最初nCounter试验中获得的候选mirna。方法：采用nCounter法进行miRNA表达谱分析，qRT-PCR验证血浆和肿瘤组织样本中的候选miRNA。对垂体肿瘤组织进行总RNA测序以鉴定转录组改变。利用泌乳素瘤细胞系分析候选miRNA靶基因及其生物学作用。结果：通过分析两组间的3组表达比较，筛选出miR-20a-5p、miR-424-5p、miR-514a-5p 3个候选miRNA。泌乳素瘤中miR-20a-5p的相对表达量明显高于正常垂体、NFPA、垂体生长激素分泌腺瘤和促肾上腺皮质激素分泌垂体腺瘤。在MMQ和GH4细胞中，miR-20a-5p抑制降低催乳素瘤细胞增殖和催乳素分泌。结论：循环miR-20a-5p是催乳素瘤的潜在生物标志物，可能与对DAs的反应性相关。

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来源期刊

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.