功能未知LncRNA RP11-290L1.3在GDM巨大儿脂肪过度积聚中的作用机制

LncRNA RP11-290L1.3, a highly conserved lncRNA in species with unknown function, was found to be significantly highly expressed in both human placentae and umbilical cord vein blood by microarray screening. Previous studies indicated that the expression level of RP11-290L1.3 was significantly increased in both trophoblast cells and culture medium under high glucose; the expression levels of RP11-290L1.3 in trophoblast cells, culture medium and birth weight were significantly positively correlated; differentiation of adipose precursor cells was dramatically promoted after RP11-290L1.3 overexpressing. Bioinformatics and experiments were performed to indicated that PHLDA1 could be a downstream target gene of RP11-290L1.3. The PHLDA1 knock-out mice showed weight gain and fat accumulation, which was consistent with the theory that placenta-derived factors and intrauterine high glucose level can lead to GDM-induced macrosomia. These clues suggested that RP11-290L1.3 may affect the expression of PHLDA1, then adipocyte differentiation and fatty deposits in the development of GDM-induced macrosomia. So far there is no reports on the roles of RP11-290L1.3 in adipose cells/tissue and its correlation with GDM-induced macrosomia. In this study, GDM rat models and human adipose precursor cells were chose to study the roles of RP11-290L1.3 in the regulation of adipocyte differentiation using overexpression/silencing methods in multilevels. Furthermore, PHLDA1 was an important clue to reveal the mechanisms of RP11-290L1.3. Given the highly conserved sequences of RP11-290L1.3 in human, mouse and rat, this study may provide a new target for prevention and treatment of GDM macrosomia.

人RP11-290L1.3（简称RP）是我们通过芯片筛选获得、同时高表达于GDM巨大儿胎盘与脐静脉血、物种间高度保守、功能未知的lncRNA。前期发现，高糖刺激后滋养细胞及培养液中RP水平显著升高；胎盘RP水平、脐静脉血RP水平、出生体重三者均显著正相关；RP过表达促进脂肪细胞分化；软件分析及实验提示PHLDA1为其靶基因；而文献报道PHLDA1基因敲除鼠体重增加、脂肪积聚，符合胎盘源性因子协同宫内高糖致GDM巨大儿的学说。鉴于脂肪积聚是GDM巨大儿的特征，提示胎盘RP可能通过调控PHLDA1影响脂肪积聚的机制致GDM巨大儿发生。迄今尚无RP与GDM巨大儿发生、脂肪积聚的研究报道。研究拟应用脂肪细胞及GDM大鼠模型，采用过表达/沉默策略，多层次阐明RP在调控脂肪积聚中的作用及与GDM巨大儿的关系；并以PHLDA1为机制线索，揭示其可能的作用机制。研究将可能为GDM巨大儿的防治提供新靶标。

人RP11-290L1.3（简称RP）是我们通过芯片筛选获得、同时高表达于GDM巨大儿胎盘与脐静脉血、物种间高度保守、功能未知的lncRNA。前期发现，高糖刺激后滋养细胞及培养液中RP水平显著升高；胎盘RP水平、脐静脉血RP水平、出生体重三者均显著正相关；RP过表达促进脂肪细胞分化；软件分析及实验提示PHLDA1为其靶基因；而文献报道PHLDA1基因敲除鼠体重增加、脂肪积聚，符合胎盘源性因子协同宫内高糖致GDM巨大儿的学说。鉴于脂肪积聚是GDM巨大儿的特征，提示胎盘RP可能通过调控PHLDA1影响脂肪积聚的机制致GDM巨大儿发生。迄今尚无RP与GDM巨大儿发生、脂肪积聚的研究报道。研究拟应用脂肪细胞及GDM大鼠模型，采用过表达/沉默策略，多层次阐明RP在调控脂肪积聚中的作用及与GDM巨大儿的关系；并以PHLDA1为机制线索，揭示其可能的作用机制。研究将可能为GDM巨大儿的防治提供新靶标。