Transcriptome sequencing of adenomyosis eutopic endometrium: A new insight into its pathophysiology

Transcriptome sequencing of adenomyosis eutopic endometrium: A new insight into its pathophysiology
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子宫腺肌病在位子宫内膜的转录组测序:对其病理生理学的新见解

DOI:
10.1111/jcmm.14718
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发表时间:
2019-10
影响因子:
5.3
通讯作者:
Xu Hong
Xu Hong
中科院分区:
医学2区
文献类型:
--
作者:
Xiang Yuqian;Sun Yabing;Yang Bingxin;Yang Yeping;Zhang Ying;Yu Tiantian;Huang Hefeng;Zhang Junyu;Xu Hong

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在位子宫内膜在子宫腺肌病的发病机制中起重要作用。然而,在位子宫内膜中与子宫腺肌病发病机制相关的特异性基因仍有待阐明。我们的目的是确定差异表达的基因(DEG)和分子通路/网络在位子宫内膜腺肌病患者,并提供一个新的见解疾病的发病机制在转录组水平。对子宫腺肌病组和对照组的12个在位子宫内膜进行RNA测序(RNA-Seq)。通过定量真实的时间PCR(qPCR)和免疫化学验证了子宫腺肌病中的差异表达基因。DEG的功能注释用免疫途径分析(IPA)进行分析。采用MassArray系统对CEBPB进行DNA甲基化定量分析。与对照组相比,共鉴定出373个子宫腺肌病在位内膜差异表达基因。生物信息学分析预测IL-6信号和ERK/MAPK信号在子宫腺肌病子宫内膜中被激活。我们还发现CEBPB的表达增加和DNA低甲基化与子宫腺肌病有关。我们的研究结果揭示了子宫腺肌病在位子宫内膜的关键通路和网络。该研究首次提出C/EBPβ与子宫腺肌病的相关性,可提高对子宫腺肌病发病机制的认识。
The eutopic endometrium has been suggested to play a crucial role in the pathogenesis of adenomyosis. However, the specific genes in eutopic endometrium responsible for the pathogenesis of adenomyosis still remain to be elucidated. We aim to identify differentially expressed genes (DEGs) and molecular pathways/networks in eutopic endometrium from adenomyosis patients and provide a new insight into disease mechanisms at transcriptome level. RNA sequencing (RNA‐Seq) was performed with 12 eutopic endometrium from adenomyosis and control groups. Differentially expressed genes in adenomyosis were validated by quantitative real‐time PCR (qPCR) and immunochemistry. Functional annotations of the DEGs were analysed with Ingenuity Pathway Analysis (IPA). Quantitative DNA methylation analysis of CEBPB was performed with MassArray system. A total of 373 differentially expressed genes were identified in the adenomyosis eutopic endometrium compared to matched controls. Bioinformatic analysis predicted that IL‐6 signalling and ERK/MAPK signalling were activated in adenomyosis endometrium. We also found that the increased expression and DNA hypomethylation of CEBPB were associated with adenomyosis. Our results revealed key pathways and networks in eutopic endometrium of adenomyosis. The study is the first to propose the association between C/EBPβ and adenomyosis and can improve the understanding of the pathogenesis of adenomyosis.
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