Up-regulation of miR-98 and unraveling regulatory mechanisms in gestational diabetes mellitus
| Autor: | Jing-Li Cao, Yi Hu, Shi Tian, Ying Li, Jian Li, Xing Su, Lu Zhang, Xiao-Dan Lv, Hong-Fei Xia, Xue-Qin Wang, Xu Ma |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Adult medicine.medical_specialty endocrine system diseases Methyl-CpG-Binding Protein 2 Placenta Type 2 diabetes Biology Article MECP2 Diabetic nephropathy 03 medical and health sciences 0302 clinical medicine Pregnancy Diabetes mellitus Internal medicine medicine Humans 3' Untranslated Regions TRPC Cation Channels Regulation of gene expression Gene knockdown Multidisciplinary Infant Newborn DNA Methylation medicine.disease Up-Regulation Gestational diabetes Diabetes Gestational MicroRNAs 030104 developmental biology Endocrinology Gene Expression Regulation 030220 oncology & carcinogenesis DNA methylation Female |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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