自发性早产孕妇血清中子宫平滑肌功能相关miRNA的表达及生物学功能分析

The serum expression and bioinformation analysis of myometrial related miRNAs for women with spontaneous preterm labor

目的 基于自发性早产子宫平滑肌中调控失常的miRNAs,寻找早产孕妇血清表达失常的miRNAs。方法 采用病例-对照研究募集2017年5月—2018年8月于复旦大学附属妇产科医院就诊的妊娠24+0周至36+6周的产妇。病例组为自发性早产的入院患者,对照组为同时期门诊产检的正常孕晚期妇女,遵循伦理原则收集和随访其临床资料和血清样本。采用定制Real-time PCR检测两组血清中子宫平滑肌功能相关的8个miRNA的表达水平,寻找早产血清中差异表达的miRNA,并通过生物信息学工具探索差异表达miRNA可能的生物学通路。结果共募集42例自发性早产孕妇(病例组)和32例非早产孕妇(对照组)。与对照组相比,miR-26b-5p和miR-936在病例组血清中的相对表达显著升高(FDR均为0.036)。生物信息分析提示:miR-26b-5p和miR-936可能通过PCNA、JARID2、PTEN和GATA4等靶分子调控血管上皮生长因子生成、细胞周期调控、磷脂酰肌醇3-激酶活性的正调节和凋亡通路等生物学通路。结论 自发性早产孕妇血清中miR-26b-5p和miR-936表达失常,血清miR-26b-5p和miR-936异常升高可能与自发性早产有关。

Objective To identify abnormal expressed serum miRNA in women with spontaneous preterm labor(sPTL) based on previously reported dysregulated miRNAs in the preterm myometrium.Methods We performed a case-control study in women without prenatal complications between 24+0 and 36+6 gestational weeks during May 2017 to Aug 2018 in Obstetrics and Gynecology Hospital of Fudan University. Pregnant women diagnosed with preterm labor were recruited as case group,women without signs of labor were recruited as control group.Clinical data and serum examples were collected under ethical principle and requirements. We evaluated a total of 8 candidate miRNAs in maternal serum by performing customized PCR analysis. We also constructed an interaction network of hub target genes of related miRNAs and their enriched gene ontology sets to explore potential biological pathways. Results A total of 74 women were recruited including 42 cases and 32 controls in this study. Compared with the control group,miR-26b-5p and miR-936 were significantly overexpressed in the maternal serum of case group(both FDR=0.036). Bioinformatics analysis indicated that miR-26b-5p and miR-936 might be involved in the progression of cell cycle regulation,cardiac muscle cell proliferation,phosphatidylinositol 3-kinase activity and apoptotic processes through target molecules such as PCNA,JARID2,PTEN and GATA4.Conclusion miR-26b-5p and miR-936 were dysregulated in the serum of women with sPTL. Increased serum levels of miR-26b-5p and miR-936 might be associated with sPTL.