Song Feiluan, Cai Anli, Ye Qianwen, Chen Xiang, Lin Lin, Hao Xi
Department of Obstetrics and Gynecology, Ruian People's Hospital, No. 108 Wansong Road, Yuhai Street, Ruian City, Wenzhou City, 325200, Zhejiang Province, China.
Biochem Genet. 2021 Dec;59(6):1381-1395. doi: 10.1007/s10528-021-10064-9. Epub 2021 Apr 15.
Gestational diabetes mellitus (GDM) leads to poor pregnancy outcomes. The methods for GDM early diagnosis and treatment are still unknown. This study aimed to investigate the expression and diagnostic potential of miR-34b-3p in GDM patients and further analyzed the effects of miR-34b-3p on HUVECs viability and migration. The expression of miR-34b-3p was detected in HUVECs of GDM and normal pregnant women by qRT-PCR. Then the HUVECs were isolated from normal pregnant women. High glucose (HG) was used to treat the HUVECs to mimic the GDM in vitro. The cell viability and migration were determined by MTT, wound healing assay, and transwell assay. The interaction between miR-34b-3p and PDK1 was evaluated by luciferase activity assay. Our results showed that miR-34b-3p was up-regulated in HUVECs of GDM patients. Then the HUVECs were isolated from normal pregnant women and they were treated with HG to mimic the GDM in vitro. Interestingly, knockdown of miR-34b-3p restored the impairment of HG treatment-induced effects in HUVECs. More importantly, PDK1 was proved to be a potential target of miR-34b-3p. Finally, the rescue experiments confirmed that miR-34b-3p impaired cell viability and migration ability in HUVECs by targeting PDK1. These findings concluded that miR-34b-3p impaired HUVECs viability and migration in GDM by targeting PDK1, which might provide a novel perspective for the pathogenesis and underlying therapeutic target for GDM.
妊娠期糖尿病（GDM）会导致不良妊娠结局。GDM的早期诊断和治疗方法仍不明确。本研究旨在探讨miR-34b-3p在GDM患者中的表达及诊断潜力，并进一步分析miR-34b-3p对人脐静脉内皮细胞（HUVECs）活力和迁移的影响。通过qRT-PCR检测GDM孕妇和正常孕妇HUVECs中miR-34b-3p的表达。然后从正常孕妇中分离出HUVECs。用高糖（HG）处理HUVECs以在体外模拟GDM。通过MTT、伤口愈合试验和Transwell试验测定细胞活力和迁移。通过荧光素酶活性试验评估miR-34b-3p与丙酮酸脱氢酶激酶1（PDK1）之间的相互作用。我们的结果表明，GDM患者HUVECs中miR-34b-3p上调。然后从正常孕妇中分离出HUVECs，并用HG处理以在体外模拟GDM。有趣的是，敲低miR-34b-3p可恢复HG处理诱导的HUVECs损伤效应。更重要的是，PDK1被证明是miR-34b-3p的潜在靶点。最后，挽救实验证实miR-34b-3p通过靶向PDK1损害HUVECs的活力和迁移能力。这些发现得出结论，miR-34b-3p通过靶向PDK1损害GDM中HUVECs的活力和迁移，这可能为GDM的发病机制和潜在治疗靶点提供新的视角。
