1International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, No. 910. Hengshan Road, Xuhui District, Shanghai, 200030 China.
2Bio-X Institutes, Shanghai Jiao Tong University, No. 800. Dongchuan Road, Minhang District, Shanghai, 200240 China.
Clin Epigenetics. 2018 Apr 10;10:48. doi: 10.1186/s13148-018-0482-3. eCollection 2018.
The etiology and pathogenesis of pre-eclampsia (PE) is unclear, and there is no ideal early clinical biomarker for prediction of PE. The competing endogenous RNA (ceRNA) hypothesis is a new approach to uncover the molecular pathology of PE. The first aim of this study was to perform messenger RNA, long non-coding RNA, and circular RNA (circRNA) expression profiling of human normal and severe pre-eclampsia (SPE) placentas. circRNA, which has a stable structure, is a more suitable biomarker than other types of RNA. Therefore, the second aim of our study was to select some differentially expressed circRNAs in PE placentas as early clinical biomarkers of PE in blood circulation.
Using microarray analysis, we investigated differentially expressed ceRNAs in human normal and SPE placentas. Bioinformatics, such as gene ontology, KEGG pathway, and ceRNA network analyses, were performed to evaluate the microarray data and gain further insights into the biological processes. RNAs (, , lnc-ELAVL4-9:1, lnc-RAP1GAP2-5:2, hsa_circ_0036877, hsa_circ_0036878, hsa_circ_0055724, hsa_circ_0049730, and hsa_circ_0036474) were validated by quantitative real-time PCR (qRT-PCR). RNA immunoprecipitation (RIP) of AGO2 in htra-8 cells and qRT-PCR analysis of hsa_circ_0036877 expression in maternal whole peripheral blood samples of participants were then conducted to confirm that hsa_circ_0036877 is a ceRNA and potential novel blood biomarker for early PE, respectively.
Our study is the first systematic profiling of ceRNAs in placentas of PE patients and revealed the global ceRNA network integration in PE. Moreover, hsa_circ_0036877 can function as a ceRNA and serve as a potential novel blood biomarker for early PE.
子痫前期（PE）的病因和发病机制尚不清楚，也没有理想的早期临床生物标志物来预测 PE。竞争内源性 RNA（ceRNA）假说为揭示 PE 的分子病理学提供了一种新方法。本研究的首要目的是对人正常和重度子痫前期（SPE）胎盘的信使 RNA、长非编码 RNA 和环状 RNA（circRNA）表达谱进行分析。circRNA 具有稳定的结构，作为一种比其他类型 RNA 更适合的生物标志物。因此，本研究的第二个目的是选择一些在 PE 胎盘中差异表达的 circRNAs 作为 PE 血液循环早期临床生物标志物。
使用微阵列分析，我们研究了人正常和 SPE 胎盘之间差异表达的 ceRNAs。通过基因本体、KEGG 通路和 ceRNA 网络分析等生物信息学方法对微阵列数据进行评估，进一步深入了解生物过程。通过定量实时 PCR（qRT-PCR）验证了 RNA（，，lnc-ELAVL4-9:1，lnc-RAP1GAP2-5:2，hsa_circ_0036877，hsa_circ_0036878，hsa_circ_0055724，hsa_circ_0049730 和 hsa_circ_0036474）。然后在 htra-8 细胞中进行 AGO2 的 RNA 免疫沉淀（RIP）和对参与者的母体全外周血样本中的 hsa_circ_0036877 表达进行 qRT-PCR 分析，以分别证实 hsa_circ_0036877 是 ceRNA 和潜在的用于早期 PE 的新型血液生物标志物。
本研究是对 PE 患者胎盘 ceRNAs 的首次系统分析，并揭示了 PE 中的全局 ceRNA 网络整合。此外，hsa_circ_0036877 可以作为 ceRNA 并作为早期 PE 的潜在新型血液生物标志物。
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