miR-200、 miR-155及血管新生因子与复发性流产的相关性分析

Correlation of miR-200, miR-155 and angiogenesis factors with recurrent spontaneous abortion

目的研究miR-200、miR-155及血管新生因子与原因不明复发性流产(unexplained recurrent spontaneous abortion,URSA)的相关性分析。方法选择2015年3月—2018年1月在青岛市妇女儿童医院妇产科就诊的URSA患者作为URSA组、要求终止妊娠的正常早孕患者作为对照组,检测绒毛组织中微小RNA(microRNA,miR)miR-200、miR-155、血管内皮生长因子(vascular endothelial growth factor,VEGF)、可溶性FMS样酪氨酸激酶1(soluble FMS like tyrosine kinase-1,sFlt-1)的表达量及血清中VEGF、sFlt-1的含量,对miR-200、miR-155靶向结合VEGF、sFlt-1进行生物信息学分析。结果URSA组的绒毛组织中miR-200(1.78±0.32 vs.0.91±0.15)、sFlt-1(1.87±0.35 vs.1.06±0.21)的相对表达量及血清中sFlt-1的含量[(12.39±2.31)ng/ml vs.(6.51±0.95)ng/ml]均高于对照组,差异有统计学意义(均P<0.05)。绒毛组织中miR-155相对表达量(0.60±0.10 vs.0.93±0.16)、VEGF mRNA相对表达量(0.59±0.09 vs.1.02±0.16)及蛋白表达量(0.62±0.07 vs.1.04±0.18)、血清中VEGF的含量[(601.25±94.39)ng/mlvs.(935.12±132.47)ng/ml]低于对照组,差异有统计学意义(均P<0.05);URSA组患者绒毛组织中miR-200的表达量与血清中VEGF的含量、绒毛组织中VEGF的表达量均呈负相关,绒毛组织中miR-155的表达量与血清中sFlt-1的含量和绒毛组织中sFlt-1的表达量均呈负相关;miR-200、miR-155分别靶向结合VEGF、sFlt-1基因的3’UTR。结论miR-200表达增多、miR-155表达减少与URSA发生有关,miR-200靶向VEGF、miR-155靶向sFlt-1是介导该过程的可能机制。

Objective To analyze the correlation of miR-200,miR-155 and angiogenic factor with unexplained recurrent spontaneous(URSA).Methods URSA patients were selected from Department of Gynecology and Obstetrics,Qingdao Women and Children’s Hospital from March 2015 to January 2018 to serve as the URSA group,and normal early pregnancy patients who required termination of pregnancy were considered as the control group.The expression of miR-200,miR-155,vascular endothelial growth factor(VEGF)and soluble FMS like tyrosine kinase-1(sFlt-1)in villus tissue and the content of serum VEGF and sFlt-1 were analyzed.Bioinformatics analysis of miR-200 and miR-155 targeting VEGF and sFlt-1 was carried out.Results The relative expression of miR-200(1.78±0.32 vs.0.91±0.15)and sFlt-1(1.87±0.35 vs.1.06±0.21)in villus tissue and the content of serum sFlt-1((12.39±2.31)ng/ml vs.(6.51±0.95)ng/ml)in the URSA group were higher than those of the control group,with statistically significant differences(both P<0.05).The relative expression of miR-155(0.60±0.10 vs.0.93±0.16),the relative expression of VEGF mRNA(0.59±0.09 vs.1.02±0.16)and protein expression(0.62±0.07 vs.1.04±0.18)in villus tissue,and the serum content of VEGF((601.25±94.39)ng/ml vs.(935.12±132.47)ng/ml)in the URSA group were all lower than those of the control group,showing statistically significant differences(all P<0.05).In the URSA group,the expression of miR-200 in villus tissue was negatively correlated with serum content of VEGF and expression of VEGF in villus tissue,while the expression of miR-155 was negatively correlated with serum content of s Flt-1 and s Flt-1 expression in villus tissue.miR-200 and miR-155 targeted the 3’-untraslated region(UTR)of VEGF and s Flt-1,respectively.Conclusions The increased expression of miR-200 and the decreased expression of miR-155 are related to the occurrence of URSA,and the targeting of miR-200 to VEGF and miR-155 to s Flt-1 is the possible mechanism.