Down-regulation of microRNA-30d-5p is associated with gestational diabetes mellitus by targeting RAB8A

• Published in: Journal of diabetes and its complications Vol. 35; no. 8; p. 107959
• Main Authors: Zhang, Lu, Li, Kai, Tian, Shi, Wang, Xue-qin, Li, Jian-hui, Dong, Yi-chao, Xia, Hong-fei, Ma, Xu
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2021; Elsevier Limited
• Subjects: Apoptosis; Cell adhesion & migration; Cell function; Cloning; Diabetes, Gestational - genetics; Down-Regulation; Female; Flow cytometry; GDM; Genes; Gestational diabetes; Glucose; Humans; Hybridization; Insulin resistance; Maternal & child health; MicroRNAs; MicroRNAs - genetics; miR-30d-5p; Obesity; Placenta; Plasmids; Pregnancy; rab GTP-Binding Proteins - genetics; RAB8A; Trophoblastic cell; GDM; miR-30d-5p; Cell function; Trophoblastic cell; RAB8A
• ISSN: 1056-8727; 1873-460X; 1873-460X
• DOI: 10.1016/j.jdiacomp.2021.107959

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. •miRNA-30d-5p are significantly downregulated in GDM patients placenta.•Human chorionic trophoblastic cells proliferation, migration and glucose uptake capacity were regulated by miR-30d-5p.•RAB8A is a direct target of miRNA-30d-5p and could regulate cell dysfunction due to the aberrant expression of miR-30d-5p.