Circular RNA hsa_circ_0000848 promotes trophoblast cell migration and invasion and inhibits cell apoptosis by sponging hsa-miR-6768-5p

To investigate the expression profiles of circRNAs in the placental tissues from pregnant women with fetal growth restriction (FGR), Arraystar Human circRNA Array V2 analysis was performed. Six samples (three samples each from FGR group and healthy controls group) were used in the microarray screening. 13532 circRNAs were identified in the placental tissues from FGR and normal groups, and only 244 circRNAs were found to be more differentially expressed in the placental tissues of the FGR group than in normal placenta (fold-change > 1.5, p < 0.05). Among them, 100 and 144 circRNAs were up- and down-regulated, respectively. To verify circRNA expression in the FGR placenta, we chose hsa_circ_0007738, hsa_circ_0071271, and hsa_circ_0000848, which have the greatest expression differences between FGR and normal groups, for further analysis. Hsa_circ_0000848 expression level was significantly lower in FGR placental tissues than in the normal placenta tissues, whereas hsa_circ_0007738 and hsa_circ_0071271 expression levels did not change significantly. Further, we found that hsa_circ_0000848 promoted trophoblast cell migration and invasion, and inhibited cell apoptosis via sponging miR-6768-5p. Firstly, microarray analysis was performed to investigate the expression profiles of circRNAs in the placental tissues from pregnant women with fetal growth restriction. Furthermore, we investigated the function and regulatory mechanism of hsa_circ_0000848 in HTR-8 cells, a human extravillous trophoblast (EVT) cell line, to study trophoblast functions including cell fusion, migration, and invasion.

为探究胎儿生长受限（fetal growth restriction, FGR）孕妇胎盘组织中环状RNA（circRNA, circular RNA）的表达谱，本研究采用Arraystar人类环状RNA芯片V2开展分析。本研究共纳入6例样本（胎儿生长受限组与健康对照组各3例）用于芯片筛选。在胎儿生长受限组与正常妊娠对照组的胎盘组织中，共鉴定得到13532条环状RNA；其中胎儿生长受限组胎盘组织中表达差异显著的环状RNA共244条（折叠变化＞1.5，P＜0.05），包括100条上调环状RNA与144条下调环状RNA。为验证环状RNA在胎儿生长受限胎盘组织中的表达特征，本研究选取了在两组间表达差异最为显著的hsa_circ_0007738、hsa_circ_0071271及hsa_circ_0000848开展后续分析。结果显示，hsa_circ_0000848在胎儿生长受限胎盘组织中的表达水平显著低于正常胎盘组织，而hsa_circ_0007738与hsa_circ_0071271的表达水平无显著变化。进一步研究发现，hsa_circ_0000848可通过海绵吸附miR-6768-5p促进滋养层细胞的迁移与侵袭，并抑制细胞凋亡。首先，本研究通过芯片分析探究了胎儿生长受限孕妇胎盘组织中环状RNA的表达谱；随后，以人绒毛外滋养层细胞系（EVT）HTR-8细胞为研究模型，对hsa_circ_0000848的功能及调控机制进行了深入探究，以解析滋养层细胞融合、迁移及侵袭等生物学过程。