LncRNA-XIST通过miR-424在生长受限儿胎盘滋养细胞迁移增殖中的作用及其机制

Fetal growth restriction (FGR) is one of the important complications in the perinatal period，and it is the second primary cause of perinatal death. Recent studies have found that placental trophoblast proliferation and migration disorders play a key role in the process of the occurrence of FGR. Pre-experimental study shown that lncRNA-XIST/miR-424/FGFR1/MEK1/MAPK pathway affect placental trophoblast cell migration and proliferation, thereby causing placental abnormalities. By appling miRNA and imprinted gene microarray, combined with bioinformatics analysis. Based on the result of case-control study, expanded sample tissue, examine the expression level of lncRNA- XIST , miR-424，target gene FGFR1 and MEK1 in the placenta tissue.adopting human trophoblast cell line (HTR-8/SVneo) cells using gene silencing and overexpression method observing human trophoblast migration proliferation, verification.lncRNA-XIST/miR-424/FGFR1/MEK1 the migration and proliferation functions in the placental trophoblast cell. in the animal model, it detect the expression of FGFR1 and MEK1, migration and proliferation in placental tissue. The project intends to clarify the lncRNA-XIST/miR-424 path way in regulation of proliferation and migration of trophoblast cell in FGR. It will provide a reference for the etiology and mechanism of FGR, and theoretical and practical basis for the prevention, diagnose and treatment of FGR.

胎儿生长受限（FGR）是围生期的重要并发症，居围生儿死亡原因第二位。近年来研究发现胎盘滋养细胞迁移增殖障碍在FGR的发生过程中起关键作用。研究组预实验应用miRNA及印记基因表达谱芯片筛选，结合生物信息学分析，提出了LncRNA-XIST/miR-424/FGFR1/MEK1/MAPK通路影响胎盘滋养细胞的迁移和增殖，进而引起胎盘发育异常的假说。本项目拟从人群病例-对照研究实验结果出发，扩大样本量，通过人滋养细胞系（HTR-8/SVneo）细胞和整体动物模型运用基因沉默和过表达技术评估lncRNA-XIST/miR-424诱发滋养细胞迁移增殖障碍参与FGR发病机制，阐明该通路在FGR滋养细胞迁移增殖障碍中的调控机制，为FGR的病因学及其机制研究提供参考，为FGR的早期预防和治疗提供理论和实践依据。

胎儿生长受限（FGR）是妊娠期重要并发症之一，是导致围生儿发病和死亡的重要原因，它不仅直接影响胎儿及新生儿的健康，也会增加其成年后对多种疾病的易感性。近年来研究发现胎盘组织长链非编码RNA（lncRNA）的异常表达与FGR的发生密切相关，项目组发现lncRNA-XIST与miR-424表达呈现正相关，靶基因MEK1和FGFR1表达呈正相关，miR-424的靶基因MEK1呈低表达状态并与miR-424的表达呈负相关，miR-424的靶基因FGFR1呈低表达状态并与miR-424的表达呈负相关，lncRNA-XIST与靶基因MEK1和 FGFR1呈负相关。本项目从病例-对照研究结果出发，研究胎盘组织中lncRNA-XIST和miR-424，及其潜在靶基因MEK1和FGFR1的表达。通过体外细胞模型研究lncRNA-XIST及miR-424异常高表达的机制及其对靶基因MEK1和FGFR1的调控作用，揭示了lncRNA-XIST及miR-424在FGR发生过程中的作用通路及细胞生物学功能，阐明其在FGR发生中的作用和分子机制。为FGR的病因学及其机制研究提供参考，为FGR的早期预防和治疗提供理论和实践依据.