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Down-regulation of microRNA-30d-5p is associated with gestational diabetes mellitus by targeting RAB8A
Journal of Diabetes and its Complications ( IF 3 ) Pub Date : 2021-05-24 , DOI: 10.1016/j.jdiacomp.2021.107959
Lu Zhang 1 , Kai Li 2 , Shi Tian 3 , Xue-Qin Wang 1 , Jian-Hui Li 1 , Yi-Chao Dong 1 , Hong-Fei Xia 1 , Xu Ma 1
Affiliation  

Gestational Diabetes Mellitus (GDM) is a complicated clinical process, and metabolic disorders during pregnancy are closely related to the structure and function of the placenta. The aberrant expression of miRNAs in the placenta may play a role in the occurrence and development of GDM. Analysis of microRNA (miRNA) expression signature in placenta showed that the level of miR-30d-5p was significantly down-regulated in GDM patients. This study aims to explore the possible mechanism of GDM under the regulation of miR-30d-5p. In situ hybridization and qRT-PCR assay showed that miR-30d expression down-regulated in the placentas from GDM patients compared with normal control group. The trophoblast cells proliferation and glucose uptake capacity were increased, the ability of migration and invasion were also improved after inhibiting the function of endogenous mature miR-30d-5p. Bioinformatics analysis and luciferase reporter assays showed that miR-30d-5p binds to the 3′UTR of RAB8A mRNA, resulting in RAB8A suppression. Moreover, the down-regulation of RAB8A could attenuate the increase in trophoblast cell proliferation, migration, invasion and glucose uptake induced by miR-30d-5p functional inhibitor. These data imply that miR-30d-5p expression is down-regulated in placental tissue from GDM patients and affects trophoblast cell functions by targeting RAB8A, which may provide new insight into the pathogenesis of GDM.



中文翻译:

通过靶向 RAB8A 下调 microRNA-30d-5p 与妊娠期糖尿病相关

妊娠期糖尿病(GDM)是一个复杂的临床过程,孕期代谢紊乱与胎盘的结构和功能密切相关。胎盘中 miRNA 的异常表达可能在 GDM 的发生和发展中发挥作用。对胎盘中 microRNA (miRNA) 表达特征的分析表明,GDM 患者中 miR-30d-5p 的水平显着下调。本研究旨在探讨GDM在miR-30d-5p调控下的可能机制。原位杂交和 qRT-PCR 分析显示,与正常对照组相比,GDM 患者胎盘中 miR-30d 的表达下调。滋养层细胞增殖和葡萄糖摄取能力增加,抑制内源性成熟miR-30d-5p的功能后,迁移和侵袭能力也得到提高。生物信息学分析和荧光素酶报告基因分析表明,miR-30d-5p 与 RAB8A mRNA 的 3'UTR 结合,导致 RAB8A 抑制。此外,RAB8A的下调可以减弱miR-30d-5p功能抑制剂诱导的滋养层细胞增殖、迁移、侵袭和葡萄糖摄取的增加。这些数据表明 miR-30d-5p 在 GDM 患者的胎盘组织中表达下调,并通过靶向 RAB8A 影响滋养层细胞功能,这可能为 GDM 的发病机制提供新的见解。RAB8A的下调可以减弱miR-30d-5p功能抑制剂诱导的滋养层细胞增殖、迁移、侵袭和葡萄糖摄取的增加。这些数据表明 miR-30d-5p 在 GDM 患者的胎盘组织中表达下调,并通过靶向 RAB8A 影响滋养层细胞功能,这可能为 GDM 的发病机制提供新的见解。RAB8A的下调可以减弱miR-30d-5p功能抑制剂诱导的滋养层细胞增殖、迁移、侵袭和葡萄糖摄取的增加。这些数据表明 miR-30d-5p 在 GDM 患者的胎盘组织中表达下调,并通过靶向 RAB8A 影响滋养层细胞功能,这可能为 GDM 的发病机制提供新的见解。

更新日期:2021-07-20
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