Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200135, China.
Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, 200135, China.
J Cell Biochem. 2018 Jan;119(1):607-615. doi: 10.1002/jcb.26221. Epub 2017 Jul 11.
Maternal decidua plays a critical role in implantation and placentation. Impaired decidualization causes failed intravascular trophoblast invasion and inadequate placentation and then increases the risk of preeclampsia (PE). RNA sequencing (RNA-Seq) has achieved great advances in the characterization and quantification of transcriptomes; is a powerful tool for new transcript discovery, genome annotation, and expression profiling. In the present study, we conducted a RNA-Seq analysis to compare gene expression between decidua of PE (n = 3, early-onset severe PE, EOSPE; n = 3, late-onset severe PE, LOSPE) and normal pregnancies (n = 3). We revealed that decidual gene transcription profile was altered in severe PE and identified 293 key PE-related genes involved in 19 differentially regulated pathways relevant for the pathogenesis of PE, among which ENO2, PGK1, and HK2 involved in glycolysis/gluconeogenesis and HIF-1 signaling pathway which are all highly related with tumorigenesis and are significantly upregulated in cancer cells were severely inhibited in the decidua of PE. Moreover, we identified 22 core regulatory genes, including the newly identified pseudogenes BNIP3P1, HK2P1, and PGK1P1 that encode long non-coding RNA (lncRNA); interestingly, BNIP3/BNIP3P1, HK2/HK2P1, and PGK1/PGK1P1 appear in pairs in core genes. Subsequent analyses using quantitative PCR validated a portion of these results. This study may provide further insight into the mechanisms of PE and function as preventive, predictive, and therapeutic measures. Future functional studies are needed in order to accomplish a greater understanding of the mechanisms involved. J. Cell. Biochem. 119: 607-615, 2018. © 2017 Wiley Periodicals, Inc.
母体蜕膜在着床和胎盘形成中起着关键作用。蜕膜化受损导致血管内滋养细胞侵袭失败和胎盘形成不足,从而增加子痫前期 (PE) 的风险。RNA 测序 (RNA-Seq) 在转录组的特征和定量方面取得了重大进展;是新转录本发现、基因组注释和表达谱分析的有力工具。在本研究中,我们进行了 RNA-Seq 分析,以比较 PE(n=3,早发型重度子痫前期,EOSPE;n=3,晚发型重度子痫前期,LOSPE)和正常妊娠(n=3)蜕膜中的基因表达。我们发现严重 PE 时蜕膜基因转录谱发生改变,并确定了 293 个与 PE 相关的关键基因,涉及与 PE 发病机制相关的 19 个差异调控途径,其中参与糖酵解/糖异生和 HIF-1 信号通路的 ENO2、PGK1 和 HK2 与肿瘤发生高度相关,在癌细胞中显著上调,在 PE 蜕膜中受到严重抑制。此外,我们鉴定了 22 个核心调控基因,包括新鉴定的假基因 BNIP3P1、HK2P1 和 PGK1P1,它们编码长非编码 RNA(lncRNA);有趣的是,BNIP3/BNIP3P1、HK2/HK2P1 和 PGK1/PGK1P1 在核心基因中成对出现。随后使用定量 PCR 进行的分析验证了其中的部分结果。本研究可能为进一步了解 PE 的机制提供了依据,并可作为预防、预测和治疗措施。未来需要进行功能研究,以更深入地了解所涉及的机制。J. Cell. Biochem. 119: 607-615, 2018. © 2017 Wiley Periodicals, Inc.