The Mechanism Of Long Non-coding RNA RP11 Promoting Adipocyte Differentiation Leading To Excessive Accumulation Of Fat In GDM Macrosomia

Aims:Gestational diabetes mellitus(GDM)-induced macrosomia is predominantly characterized by fat accumulation,which is closely related to adipocyte differentiation.An unknown long noncoding RNA RP11-290L1.3,referred to as RP11,was identified to be dramatically upregulated in the umbilical cord blood of women with GDM-induced macrosomia in our previous study.We conducted this study to identify the function of lncRNA RP11-290L1.3 in GDM-induced macrosomia.Methods:According to the diagnostic criteria of the 9^thedition of textbook,79umbilical cord blood samples were collected from pregnant women who delivered babies in Nanjing Maternity And Child Health Care Hospital.And they were divided into two groups,non-macrosomia group of normal pregnancy(47 cases)and pregnant women in the GDM macrosomia group(32 cases).Pearson's correlation coefficient analysis was used to analyze the correlation between the relative expression of RP11 and neonatal birth weight,F%,or FM in the umbilical cord blood of 79 subjects.The effects of lncRNA RP11-290L1.3 gain-and loss-of-function on HPA-v(human preadipocytes-visceral)adipogenesis were determined with lentivirus mediated cell transduction.The RNA and protein expression levels of adipogenesis makers were evaluated by q PCR/western blot.Cell proliferation assay of the HPA-v was performed using the flow cytometry.And oil red O staining was used to evaluate the differentiation of adipocytes.Then,we performed the Microarray and pathway analysis to explore the possible mechanisms by which lncRNA RP11-290L1.3regulates adipogenesis.Results:Pearson's correlation coefficient analysis suggested a significant positive correlation between RP11 expression and neonatal birth weight(r=0.8003),F%(r=0.7999)and FM(r=0.8150).Overexpression of lncRNA RP11-290L1.3 significantly enhanced adipocyte differentiation and increased the RNA and protein expression levels of adipogenesis makers,such as PPAR-?,SREBP1c,and FASN by q PCR/western blot.Knockdown of lncRNA RP11-290L1.3 showed opposite effects.Microarray and pathway analysis showed,after lncRNA RP11-290L1.3 knockdown,1,612 genes were upregulated and 583 genes were downregulated which were found to be mainly involved in metabolic pathways,insulin signaling pathway and MAPK signaling pathway.Conclusion:In conclusion,the unknown lncRNA RP11-290L1.3 serves a positive factor on preadipocyte differentiation which could shed light on fetal fat accumulation in GDM.