Up-regulation of miR-98 and unraveling regulatory mechanisms in gestational diabetes mellitus

作者：Jingli Cao, Lu Zhang, Jian Li, Tian Shi, Xiaodan Lv, Xueqin Wang, Xing Su, Ying Li, Yi Hu, Xu Ma, Hong-Fei Xia · 发表于：Scientific Reports · 年份：2016 · DOI：10.1038/srep32268 · 被引用次数：55 · 研究领域：MicroRNA in disease regulation、Pregnancy and preeclampsia studies、Cancer-related molecular mechanisms research

MiR-98 expression was up-regulated in kidney in response to early diabetic nephropathy in mouse and down-regulated in muscle in type 2 diabetes in human. However, the expression prolife and functional role of miR-98 in human gestational diabetes mellitus (GDM) remained unclear. Here, we investigated its expression and function in placental tissues from GDM patients and the possible molecular mechanisms. The results showed that miR-98 was up-regulated in placentas from GDM patients compared with normal placentas. MiR-98 over-expression increased global DNA methylational level and miR-98 knockdown reduced global DNA methylational level. Further investigation revealed that miR-98 could inhibit Mecp2 expression by binding the 3'-untranslated region (UTR) of methyl CpG binding protein 2 (Mecp2), and then led to the expression dysregulation of canonical transient receptor potential 3 (Trpc3), a glucose uptake related gene. More importantly, in vivo analysis found that the expression level of Mecp2 and Trpc3 in placental tissues from GDM patients, relative to the increase of miR-98, was diminished, especially for GDM patients over the age of 35 years. Collectively, up-regulation of miR-98 in the placental tissues of human GDM is linked to the global DNA methylation via targeting Mecp2, which may imply a novel regulatory mechanism in GDM.