title: Up-regulation of miR-98 and unraveling regulatory mechanisms in gestational diabetes mellitus.
abstract: 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.
authors: Reproductive and Genetic Center of National Research Institute for Family Planning, Beijing, 100081, China.|Graduate School, Peking Union Medical College, Beijing, 100730, China.
authors: Jing-Li
authors: JL
authors: Cao
authors: Reproductive and Genetic Center of National Research Institute for Family Planning, Beijing, 100081, China.|Graduate School, Peking Union Medical College, Beijing, 100730, China.
authors: Lu
authors: L
authors: Zhang
authors: Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing, 100029, China.
authors: Jian
authors: J
authors: Li
authors: Maternal and Child Health Hospital, Haidian District, Beijing, 100080, China.
authors: Shi
authors: S
authors: Tian
authors: Reproductive and Genetic Center of National Research Institute for Family Planning, Beijing, 100081, China.|Graduate School, Peking Union Medical College, Beijing, 100730, China.
authors: Xiao-Dan
authors: XD
authors: Lv
authors: Reproductive and Genetic Center of National Research Institute for Family Planning, Beijing, 100081, China.|Graduate School, Peking Union Medical College, Beijing, 100730, China.
authors: Xue-Qin
authors: XQ
authors: Wang
authors: Reproductive and Genetic Center of National Research Institute for Family Planning, Beijing, 100081, China.|Graduate School, Peking Union Medical College, Beijing, 100730, China.
authors: Xing
authors: X
authors: Su
authors: Reproductive and Genetic Center of National Research Institute for Family Planning, Beijing, 100081, China.|Graduate School, Peking Union Medical College, Beijing, 100730, China.
authors: Ying
authors: Y
authors: Li
authors: Reproductive and Genetic Center of National Research Institute for Family Planning, Beijing, 100081, China.|Graduate School, Peking Union Medical College, Beijing, 100730, China.
authors: Yi
authors: Y
authors: Hu
authors: Reproductive and Genetic Center of National Research Institute for Family Planning, Beijing, 100081, China.|Graduate School, Peking Union Medical College, Beijing, 100730, China.
authors: Xu
authors: X
authors: Ma
authors: Reproductive and Genetic Center of National Research Institute for Family Planning, Beijing, 100081, China.|Graduate School, Peking Union Medical College, Beijing, 100730, China.
authors: Hong-Fei
authors: HF
authors: Xia
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000328:Adult; D019175:DNA Methylation; D016640:Diabetes, Gestational / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007231:Infant, Newborn; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D050052:TRPC Cation Channels / Q000235:genetics; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; C497392:MECP2 protein, human; C546084:MIRN98 microRNA, human; D051783:Methyl-CpG-Binding Protein 2; D035683:MicroRNAs; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel