title: Differential expression of microRNAs in omental adipose tissue from gestational diabetes mellitus subjects reveals miR-222 as a regulator of ERα expression in estrogen-induced insulin resistance.
abstract: Omental adipose tissue plays a central role in insulin resistance in gestational diabetes mellitus (GDM), and the molecular mechanisms leading to GDM remains vague. Evidence demonstrates that maternal hormones, such as estradiol, contribute to insulin resistance in GDM. In this study we determined the differential expression patterns of microRNAs (miRNAs) in omental adipose tissues from GDM patients and pregnant women with normal glucose tolerance using AFFX miRNA expression chips. MiR-222, 1 of 17 identified differentially expressed miRNAs, was found to be significantly up-regulated in GDM by quantitative real-time PCR (P < .01), and its expression was closely related with serum estradiol level (P < .05). Furthermore, miR-222 expression was significantly increased in 3T3-L1 adipocytes with a high concentration of 17β-estradiol stimulation (P < .01), whereas the expressions of estrogen receptor (ER)-α protein and insulin-sensitive membrane transporter glucose transporter 4 (GLUT4) protein (P < .01) were markedly reduced. In addition, ERα was shown to be a direct target of miR-222 in 3T3-L1 adipocytes by using the luciferase assay. Finally, antisense oligonucleotides of miR-222 transfection was used to silence miR-222 in 3T3-L1 adipocytes. The results showed that the expressions of ERα and GLUT4, the insulin-stimulated translocation of GLUT4 from the cytoplasm to the cell membrane and glucose uptake in mature adipocytes were dramatically increased (P < .01). In conclusion, miR-222 is a potential regulator of ERα expression in estrogen-induced insulin resistance in GDM and might be a candidate biomarker and therapeutic target for GDM.
authors.affiliation: State Key Laboratory of Reproductive Medicine (Y.C., J.L.), Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, People's Republic of China; and Department of Obstetrics (Z.S., C.Z., X.G., H.D., R.S.), Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University, Nanjing 210004, People's Republic of China.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Shi
authors.forename: Chun
authors.initials: C
authors.lastname: Zhao
authors.forename: Xirong
authors.initials: X
authors.lastname: Guo
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Ding
authors.forename: Yugui
authors.initials: Y
authors.lastname: Cui
authors.forename: Rong
authors.initials: R
authors.lastname: Shen
authors.forename: Jiayin
authors.initials: J
authors.lastname: Liu
mesh_terms: D041721:3T3-L1 Cells; D000328:Adult; D000818:Animals; D002585:Cesarean Section; D016640:Diabetes, Gestational / Q000097:blood / Q000378:metabolism*; D004958:Estradiol / Q000097:blood / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D017930:Genes, Reporter; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis* / Q000378:metabolism; D050505:Mutant Proteins / Q000378:metabolism; D011247:Pregnancy; D021381:Protein Transport; D047929:Term Birth; D014162:Transfection; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D004958:Estradiol; D047628:Estrogen Receptor alpha; D051275:Glucose Transporter Type 4; D007328:Insulin; D035683:MicroRNAs; D050505:Mutant Proteins; C506487:ESR1 protein, human; C525710:MIR222, human; C495692:SLC2A4 protein, human