title: Reactive oxygen species regulate ERBB2 and ERBB3 expression via miR-199a/125b and DNA methylation.
abstract: Overexpression of ERBB2 or ERBB3 is associated with cancer development and poor prognosis. In this study, we show that reactive oxygen species (ROS) induce both ERBB2 and ERBB3 expression in vitro and in vivo. We also identify that miR-199a and miR-125b target ERBB2 and/or ERBB3 in ovarian cancer cells, and demonstrate that ROS inhibit miR-199a and miR-125b expression through increasing the promoter methylation of the miR-199a and miR-125b genes by DNA methyltransferase 1. These findings reveal that ERBB2 and ERBB3 expression is regulated by ROS via miR-199a and miR-125b downregulation and DNA hypermethylation.
authors.affiliation: State Key Lab of Reproductive Medicine, Department of Pathology, Cancer Center, Nanjing Medical University, Nanjing 210029, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: He
authors.forename: Qing
authors.initials: Q
authors.lastname: Xu
authors.forename: Yi
authors.initials: Y
authors.lastname: Jing
authors.forename: Faton
authors.initials: F
authors.lastname: Agani
authors.forename: Xu
authors.initials: X
authors.lastname: Qian
authors.forename: Richard
authors.initials: R
authors.lastname: Carpenter
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.forename: Xin-Ru
authors.initials: XR
authors.lastname: Wang
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Peiper
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Lu
authors.forename: Ling-Zhi
authors.initials: LZ
authors.lastname: Liu
authors.forename: Bing-Hua
authors.initials: BH
authors.lastname: Jiang
mesh_terms: D000482:Allantois / Q000254:growth & development; D000818:Animals; D045744:Cell Line, Tumor / Q000187:drug effects; D002645:Chickens; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects; D005260:Female; D005452:Fluoresceins / Q000737:chemistry / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000737:chemistry / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D020893:Receptor, ErbB-3 / Q000235:genetics*
chemical_list: D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D005452:Fluoresceins; D035683:MicroRNAs; D017382:Reactive Oxygen Species; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; C531888:MIRN125 microRNA, human; C531408:mirn199 microRNA, human; C029569:diacetyldichlorofluorescein; C508053:ERBB2 protein, human; C581292:ERBB3 protein, human