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探索子宫内膜异位症中的诊断 m6A 调节剂。

Exploring diagnostic m6A regulators in endometriosis.

机构信息

Department of Obstetrics and Gynecology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

出版信息

Aging (Albany NY). 2020 Nov 24;12(24):25916-25938. doi: 10.18632/aging.202163.

Abstract

Endometriosis is an estrogen-dependent inflammatory disorder, usually causing infertility, pelvic pain, and ovarian masses. This study intended to investigate the implication of N6-methyladenosine (m6A) regulators in endometriosis. We acquired 34 normal, 127 eutopic, and 46 ectopic, samples of endometrium from the Gene Expression Omnibus (GSE7305, GSE7307, GSE51981) database and the Array-express (E-MTAB-694) database. These samples were then used to profile the expression of 20 m6A regulators in endometriosis. The results indicated that most dysregulated (19/20) m6A regulators were significantly downregulated in eutopic normal endometrium and also significantly downregulated in ectopic eutopic endometrium. Several dysregulated m6A regulators were common to both contrast matrices: METTL3, YTHDF2, YTHDF3, HNRNPA2B1, HNRNPC, and FTO. Both HNRNPA2B1 and HNRNPC were associated with the severity of endometriosis in eutopic samples, and also exhibited diagnostic potential for endometriosis. HNRNPA2B1 and HNRNPC may influence immune pathways and the infiltration of immune cells in endometriosis. Abnormalities in the gene transcription factors network associated with endometriosis might affect the expression of HNRNPA2B1 and HNRNPC. In conclusion, we observed significant dysregulation of m6A regulators in endometriosis, and found that HNRNPA2B1 and HNRNPC might correlate with the immune response and serve as useful diagnostic biomarkers for endometriosis.

摘要

子宫内膜异位症是一种雌激素依赖性炎症性疾病,通常导致不孕、盆腔疼痛和卵巢肿块。本研究旨在探讨 N6-甲基腺苷(m6A)调节剂在子宫内膜异位症中的作用。我们从基因表达综合数据库(GSE7305、GSE7307、GSE51981)和 Array-express 数据库(E-MTAB-694)中获得了 34 个正常、127 个在位和 46 个异位子宫内膜样本,用于分析 20 种 m6A 调节剂在子宫内膜异位症中的表达谱。结果表明,大多数失调的(19/20)m6A 调节剂在正常在位内膜中显著下调,在异位在位内膜中也显著下调。几个失调的 m6A 调节剂在两个对照矩阵中是共同的:METTL3、YTHDF2、YTHDF3、HNRNPA2B1、HNRNPC 和 FTO。HNRNPA2B1 和 HNRNPC 均与在位样本中子宫内膜异位症的严重程度相关,且对子宫内膜异位症具有诊断潜力。HNRNPA2B1 和 HNRNPC 可能影响子宫内膜异位症中的免疫途径和免疫细胞浸润。与子宫内膜异位症相关的基因转录因子网络的异常可能影响 HNRNPA2B1 和 HNRNPC 的表达。总之,我们观察到子宫内膜异位症中 m6A 调节剂的显著失调,发现 HNRNPA2B1 和 HNRNPC 可能与免疫反应相关,并可作为子宫内膜异位症的有用诊断生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fee/7803542/765a5dd279f6/aging-12-202163-g001.jpg

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