Department of Obstetrics and Gynaecology, Peking University Third Hospital, Beijing, China.
Department of Obstetrics and Gynaecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J Cell Biochem. 2020 Jan;121(1):713-722. doi: 10.1002/jcb.29317. Epub 2019 Aug 5.
Small for gestational age (SGA) has a high risk of mortality and morbidity and is common in obstetrics. To date, no effective prediction and treatment tools are available. Acting as microRNA (miRNA) sponges and disease biomarkers are clear functions of circular RNAs (circRNAs). However, it is still unknown what role circRNAs act in SGA. To explore the role of circRNAs in SGA, circRNA expression patterns of the umbilical cord and maternal plasma in SGA was assessed. We first evaluated circRNAs in umbilical cord blood of the SGA and appropriate for gestational age (AGA) groups by microarray sequencing. In total, 170 340 circRNAs were sequenced, and 144 circRNAs were significantly upregulated while 977 were markedly downregulated. Has_circRNA15994-13, has_circ_0001359, and has_circ_0001360 were abundant and differentially expressed between the SGA and AGA groups, and confirmed in the umbilical cord and maternal blood specimens by reverse transcription polymerase chain reaction. By combining miRNA microarray data of the SGA placenta tissue in NCBI, it was found that two miRNAs were both hsa_circRNA15994-13 targets and differentially expressed, including hsa-miR-3619-5p and hsa-miR-4741. Further KEEG analysis revealed that the most significant pathway enriched by hsa-miR-3619-5p was Wnt signaling that is closely related to SGA; meanwhile, previous reports demonstrated that hsa-miR-3619-5p directly binds to β-catenin to accommodate the Wnt/β-catenin pathway, whereby the suggestive hsa_circRNA15994-13 → hsa-miR-3619-5p → β-catenin signaling pathway may play an important part in SGA.
胎儿生长受限（SGA）具有较高的死亡率和发病率，在产科中较为常见。迄今为止，尚无有效的预测和治疗工具。环状 RNA（circRNA）作为 microRNA（miRNA）海绵和疾病生物标志物的功能已得到明确证实。然而，circRNA 在 SGA 中的作用尚不清楚。为了探讨 circRNA 在 SGA 中的作用，我们评估了 SGA 脐带和母体血浆中 circRNA 的表达模式。我们首先通过微阵列测序评估了 SGA 和适当胎龄（AGA）组脐带血中的 circRNA。总共测序了 170340 个 circRNA，其中 144 个 circRNA 显著上调，977 个 circRNA 显著下调。在 SGA 和 AGA 组之间，has_circRNA15994-13、has_circ_0001359 和 has_circ_0001360 丰度高且差异表达，并通过逆转录聚合酶链反应在脐带和母血标本中得到验证。通过结合 NCBI 中 SGA 胎盘组织的 miRNA 微阵列数据，发现有两个 miRNA 都是 hsa_circRNA15994-13 的靶标且差异表达，包括 hsa-miR-3619-5p 和 hsa-miR-4741。进一步的 KEEG 分析显示，hsa-miR-3619-5p 富集的最显著通路是与 SGA 密切相关的 Wnt 信号通路；同时，先前的报道表明，hsa-miR-3619-5p 直接与β-catenin 结合以容纳 Wnt/β-catenin 通路，提示 hsa_circRNA15994-13→hsa-miR-3619-5p→β-catenin 信号通路可能在 SGA 中发挥重要作用。
