Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Institute of Embryo-Fetal Original Adult Disease, Affiliated to School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Reproduction. 2019 Jun;157(6):525-534. doi: 10.1530/REP-18-0631.
MicroRNA (miRNA) expression profiles in tubal endometriosis (EM) are still poorly understood. In this study, we analyzed the differential expression of miRNAs and the related gene networks and signaling pathways in tubal EM. Four tubal epithelium samples from tubal EM patients and five normal tubal epithelium samples from uterine leiomyoma patients were collected for miRNA microarray. Bioinformatics analyses, including Ingenuity Pathway Analysis (IPA), Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, were performed. Quantitative real-time polymerase chain reaction (qRT-PCR) validation of five miRNAs was performed in six tubal epithelium samples from tubal EM and six from control. A total of 17 significantly differentially expressed miRNAs and 4343 potential miRNA-target genes involved in tubal EM were identified (fold change >1.5 and FDR-adjusted P value <0.05). IPA indicated connections between miRNAs, target genes and other gynecological diseases like endometrial carcinoma. GO and KEGG analysis revealed that most of the identified genes were involved in the mTOR signaling pathway, SNARE interactions in vesicular transport and endocytosis. We constructed an miRNA-gene-disease network using target gene prediction. Functional analysis showed that the mTOR pathway was connected closely to tubal EM. Our results demonstrate for the first time the differentially expressed miRNAs and the related signal pathways involved in the pathogenesis of tubal EM which contribute to elucidating the pathogenic mechanism of tubal EM-related infertility.
输卵管子宫内膜异位症（EM）中的 microRNA（miRNA）表达谱仍知之甚少。在这项研究中，我们分析了输卵管 EM 中 miRNA 的差异表达及其相关基因网络和信号通路。收集了 4 例输卵管 EM 患者的输卵管上皮组织样本和 5 例子宫肌瘤患者的正常输卵管上皮组织样本进行 miRNA 微阵列分析。进行了生物信息学分析，包括Ingenuity Pathway Analysis（IPA）、基因本体论（GO）分析和京都基因与基因组百科全书（KEGG）通路分析。在 6 例输卵管 EM 和 6 例对照的输卵管上皮组织样本中对 5 个 miRNA 进行了定量实时聚合酶链反应（qRT-PCR）验证。鉴定出 17 个显著差异表达的 miRNA 和 4343 个与输卵管 EM 相关的潜在 miRNA 靶基因（倍数变化>1.5，FDR 调整 P 值<0.05）。IPA 表明 miRNA、靶基因与子宫内膜癌等其他妇科疾病之间存在联系。GO 和 KEGG 分析表明，大多数鉴定出的基因参与 mTOR 信号通路、囊泡运输和内吞作用中的 SNARE 相互作用。我们使用靶基因预测构建了 miRNA-基因-疾病网络。功能分析表明 mTOR 通路与输卵管 EM 密切相关。我们的研究结果首次证明了参与输卵管 EM 发病机制的差异表达 miRNA 和相关信号通路，有助于阐明输卵管 EM 相关不孕的发病机制。
