Suppr超能文献

辛伐他汀调控子宫内膜异位症灵长类模型血清 microRNA 生物标志物的研究

Serum MicroRNA Biomarkers Regulated by Simvastatin in a Primate Model of Endometriosis.

机构信息

Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA.

Division of Reproductive Endocrinology and Infertility, Department of Reproductive Medicine, University of California, San Diego, CA, USA.

出版信息

Reprod Sci. 2019 Oct;26(10):1343-1350. doi: 10.1177/1933719118765971. Epub 2018 Mar 27.

Abstract

Endometriosis is a chronic inflammatory and estrogen-dependent disease that causes pain and infertility in reproductive-aged women. Due to the delay in diagnosis, there is a pressing need for accurate biomarkers. Detection of serum noncoding RNA molecules such as microRNAs (miRNAs) shows promise as a noninvasive diagnostic strategy; we previously identified miRNAs that are highly sensitive and specific biomarkers for the disease. In this study, we investigate the expression of these miRNAs in a nonhuman primate model of endometriosis. As part of a pilot study evaluating simvastatin for the treatment of endometriosis, the disease was induced in 16 baboons by induction laparoscopy and the animals were divided into 2 groups. One group was treated with simvastatin for 90 days, while the second group received vehicle only. Endometriosis was evaluated after 3 months by laparoscopy. Serum samples were analyzed for 9 circulating miRNAs using quantitative real time-polymerase chain reaction, focusing on the miRNAs we found to be dysregulated in human endometriosis. In the simvastatin-treated endometriosis group, levels of miR-150-5p and miR-451a were decreased, while miR-3613-5p levels were increased compared to the untreated endometriosis group. The changes in circulating miRNA expression patterns parallel our previous results in human patients and show that specific miRNAs correlate with endometriosis severity and reverted toward control expression levels after simvastatin treatment. This is the first report showing serum miRNA expression normalized in response to endometriosis treatment, supporting the potential for this class of biomarkers to be used both to diagnose endometriosis and to monitor its progression and response to therapy.

摘要

子宫内膜异位症是一种慢性炎症性和雌激素依赖性疾病,会导致生殖期妇女出现疼痛和不孕。由于诊断延误,因此迫切需要准确的生物标志物。检测血清非编码 RNA 分子,如 microRNAs(miRNAs),作为一种非侵入性诊断策略具有很大的前景;我们之前已经确定了一些 miRNA 是该疾病高度敏感和特异的生物标志物。在这项研究中,我们研究了这些 miRNA 在子宫内膜异位症的非人类灵长类动物模型中的表达情况。作为评估辛伐他汀治疗子宫内膜异位症的初步研究的一部分,通过腹腔镜诱导在 16 只狨猴中诱发疾病,将动物分为两组。一组用辛伐他汀治疗 90 天,而另一组仅用载体治疗。3 个月后通过腹腔镜评估子宫内膜异位症。使用定量实时聚合酶链反应分析 9 种循环 miRNA 的血清样本,重点关注我们在人类子宫内膜异位症中发现失调的 miRNA。在辛伐他汀治疗的子宫内膜异位症组中,miR-150-5p 和 miR-451a 的水平降低,而 miR-3613-5p 的水平与未治疗的子宫内膜异位症组相比升高。循环 miRNA 表达模式的变化与我们在人类患者中的先前结果一致,表明特定的 miRNA 与子宫内膜异位症的严重程度相关,并在辛伐他汀治疗后恢复到对照表达水平。这是第一个表明血清 miRNA 表达正常化以响应子宫内膜异位症治疗的报告,支持了这类生物标志物用于诊断子宫内膜异位症以及监测其进展和对治疗的反应的潜力。

相似文献

1
Serum MicroRNA Biomarkers Regulated by Simvastatin in a Primate Model of Endometriosis.
Reprod Sci. 2019 Oct;26(10):1343-1350. doi: 10.1177/1933719118765971. Epub 2018 Mar 27.
2
Accurate diagnosis of endometriosis using serum microRNAs.
Am J Obstet Gynecol. 2020 Oct;223(4):557.e1-557.e11. doi: 10.1016/j.ajog.2020.02.050. Epub 2020 Mar 9.
5
MicroRNAs in endometriosis: biological function and emerging biomarker candidates†.
Biol Reprod. 2019 May 1;100(5):1135-1146. doi: 10.1093/biolre/ioz014.
6
Circulating serum miR-200c and miR-34a-5p as diagnostic biomarkers for endometriosis.
J Gynecol Obstet Hum Reprod. 2021 Apr;50(4):102092. doi: 10.1016/j.jogoh.2021.102092. Epub 2021 Feb 15.
7
Serum microRNAs as diagnostic markers of endometriosis: a comprehensive array-based analysis.
Fertil Steril. 2016 Aug;106(2):402-9. doi: 10.1016/j.fertnstert.2016.04.013. Epub 2016 May 11.
8
Circulating miRNAs in Murine Experimental Endometriosis.
Reprod Sci. 2017 Mar;24(3):376-381. doi: 10.1177/1933719116667228. Epub 2016 Sep 27.
9
Circulating microRNAs identified in a genome-wide serum microRNA expression analysis as noninvasive biomarkers for endometriosis.
J Clin Endocrinol Metab. 2013 Jan;98(1):281-9. doi: 10.1210/jc.2012-2415. Epub 2012 Nov 1.
10
Plasma miRNAs as biomarkers for endometriosis.
Hum Reprod. 2019 Sep 29;34(9):1650-1660. doi: 10.1093/humrep/dez116.

引用本文的文献

1
Salsalate negatively impacts microvascular function in women with endometriosis.
Am J Physiol Heart Circ Physiol. 2025 Apr 1;328(4):H915-H922. doi: 10.1152/ajpheart.00012.2025. Epub 2025 Mar 6.
2
The Known, the Unknown and the Future of the Pathophysiology of Endometriosis.
Int J Mol Sci. 2024 May 27;25(11):5815. doi: 10.3390/ijms25115815.
4
Circulating miR-27b as a Biomarker of the Development and Progression of Carotid Artery Stenosis.
Clin Appl Thromb Hemost. 2021 Jan-Dec;27:10760296211057903. doi: 10.1177/10760296211057903.
5
A critical appraisal of the circulating levels of differentially expressed microRNA in endometriosis†.
Biol Reprod. 2021 Nov 15;105(5):1075-1085. doi: 10.1093/biolre/ioab134.
6
A Novel Prognostic Model of Endometrial Carcinoma Based on Clinical Variables and Oncogenomic Gene Signature.
Front Mol Biosci. 2021 Jan 7;7:587822. doi: 10.3389/fmolb.2020.587822. eCollection 2020.
7
miR-3613-5p enhances the metastasis of pancreatic cancer by targeting CDK6.
Cell Cycle. 2020 Nov;19(22):3086-3095. doi: 10.1080/15384101.2020.1831254. Epub 2020 Oct 19.
8
Role of Non-coding RNAs in the Pathogenesis of Endometriosis.
Front Oncol. 2020 Aug 4;10:1370. doi: 10.3389/fonc.2020.01370. eCollection 2020.

本文引用的文献

1
Tumor suppressor activity of miR-451: Identification of CARF as a new target.
Sci Rep. 2018 Jan 10;8(1):375. doi: 10.1038/s41598-017-18559-5.
2
MiR-3613-3p affects cell proliferation and cell cycle in hepatocellular carcinoma.
Oncotarget. 2017 Oct 10;8(54):93014-93028. doi: 10.18632/oncotarget.21745. eCollection 2017 Nov 3.
3
miR-342-3p suppresses cell proliferation and migration by targeting AGR2 in non-small cell lung cancer.
Cancer Lett. 2018 Jan 1;412:170-178. doi: 10.1016/j.canlet.2017.10.024. Epub 2017 Nov 5.
4
MicroRNA-150 promotes cell proliferation, migration, and invasion of cervical cancer through targeting PDCD4.
Biomed Pharmacother. 2018 Jan;97:511-517. doi: 10.1016/j.biopha.2017.09.143. Epub 2017 Nov 6.
6
Circulating microRNAs in breast cancer: novel diagnostic and prognostic biomarkers.
Cell Death Dis. 2017 Sep 7;8(9):e3045. doi: 10.1038/cddis.2017.440.
7
Challenges in endometriosis miRNA studies - From tissue heterogeneity to disease specific miRNAs.
Biochim Biophys Acta Mol Basis Dis. 2017 Sep;1863(9):2282-2292. doi: 10.1016/j.bbadis.2017.06.018. Epub 2017 Jun 23.
8
Effect of simvastatin on baboon endometriosis.
Biol Reprod. 2017 Jul 1;97(1):32-38. doi: 10.1093/biolre/iox058.
9
Treatment of Endometriosis-Associated Pain with Elagolix, an Oral GnRH Antagonist.
N Engl J Med. 2017 Jul 6;377(1):28-40. doi: 10.1056/NEJMoa1700089. Epub 2017 May 19.
10
MicroRNA-500a promotes migration and invasion in hepatocellular carcinoma by activating the Wnt/β-catenin signaling pathway.
Biomed Pharmacother. 2017 Jul;91:13-20. doi: 10.1016/j.biopha.2017.04.018. Epub 2017 Apr 22.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验