Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Chin Med J (Engl). 2018 Mar 5;131(5):559-566. doi: 10.4103/0366-6999.226070.
Endometriosis is a challenging disease with symptoms such as dysmenorrhea and infertility. However, its etiology is still vague and there is still no effective markers or treatment. This study aimed to profile the circular RNAs (circRNAs) expressed in eutopic endometrium from patients with ovarian endometriosis and explore potential clues to the pathogenesis of endometriosis, providing an evidence for clinical diagnosis and treatment.
A total of 63 clinical samples, including control endometrium (n = 22) and eutopic endometrium (n = 41), were collected from Peking Union Medical College Hospital between May 1, 2016, and December 31, 2016. Of them, four samples in each group were used for circRNA microarray. Then, four upregulated circRNAs were screened out for quantitative real-time polymerase chain reaction (qRT-PCR) validation. After that, bioinformatics analysis was performed to predict miRNAs targeted by validated circRNAs and investigate the circRNA-miRNA-mRNA interactions.
Among 88 differentially expressed circRNAs, 11 were upregulated and 77 were downregulated in eutopic endometrium of patients with endometriosis. qRT-PCR validation results for two upregulated circRNAs (circ_0004712 and circ_0002198) matched the microarray results. The area under the receiver operating characteristic curve of circ_0002198 for distinguishing ovarian endometriosis was 0.846 (95% confidence interval [CI]: 0.752-0.939; P < 0.001) while that of circ_0004712 was 0.704 (95% CI: 0.571-0.837; P = 0.008). On the basis of target prediction, we depicted the molecular interactions between the identified circRNAs and their dominant target miRNAs, as well as constructed a circRNA-miRNA-mRNA network.
This study provides evidence that circRNAs are differentially expressed between eutopic and normal endometrium, which suggests that circRNAs are candidate factors in the activation of endometriosis. circ_0002198 and circ_0004712 may be potential novel biomarkers for the diagnosis of ovarian endometriosis.
子宫内膜异位症是一种具有痛经和不孕等症状的棘手疾病。然而，其病因仍不清楚，也没有有效的标志物或治疗方法。本研究旨在分析卵巢子宫内膜异位症患者在位子宫内膜中表达的环状 RNA（circRNA），并探讨其发病机制的潜在线索，为临床诊断和治疗提供依据。
本研究于 2016 年 5 月 1 日至 12 月 31 日期间共收集了 63 例临床样本，包括对照组子宫内膜（n=22）和在位子宫内膜（n=41）。其中每组各有 4 例样本用于 circRNA 微阵列分析。然后，筛选出 4 个上调的 circRNA 进行定量实时聚合酶链反应（qRT-PCR）验证。之后，进行生物信息学分析以预测经验证的 circRNA 靶向的 miRNA，并研究 circRNA-miRNA-mRNA 相互作用。
在 88 个差异表达的 circRNA 中，11 个在子宫内膜异位症患者的在位子宫内膜中上调，77 个下调。两个上调的 circRNA（circ_0004712 和 circ_0002198）的 qRT-PCR 验证结果与微阵列结果相符。circ_0002198 区分卵巢子宫内膜异位症的受试者工作特征曲线下面积为 0.846（95%置信区间[CI]：0.752-0.939；P<0.001），circ_0004712 为 0.704（95%CI：0.571-0.837；P=0.008）。基于靶标预测，我们描绘了鉴定出的 circRNA 与其主要靶 miRNA 之间的分子相互作用，并构建了 circRNA-miRNA-mRNA 网络。
本研究提供了证据表明，circRNA 在在位和正常子宫内膜之间存在差异表达，这表明 circRNA 是子宫内膜异位症激活的候选因素。circ_0002198 和 circ_0004712 可能是卵巢子宫内膜异位症诊断的潜在新型生物标志物。
