title: MicroRNA-21 modulates the levels of reactive oxygen species by targeting SOD3 and TNFα.
abstract: MicroRNA-21 (miR-21) is an oncomir overexpressed in most human tumors in that it promotes malignant growth and progression by acting on multiple targets. Here, we broaden the impact of miR-21 in cancer by showing that it regulates the formation of reactive oxygen species (ROS) that promote tumorigenesis. Key targets of miR-21 in mediating this function were SOD3 and TNFα. We found that miR-21 inhibited the metabolism of superoxide to hydrogen peroxide, produced either by endogenous basal activities or exposure to ionizing radiation (IR), by directing attenuating SOD3 or by an indirect mechanism that limited TNFa production, thereby reducing SOD2 levels. Importantly, both effects contributed to an elevation of IR-induced cell transformation. Our findings, therefore, establish that miR-21 promotes tumorigenesis to a large extent through its regulation of cellular ROS levels.
authors: Department of Radiation Oncology, Winship Cancer Institute, Emory University School of Medicine, Emory University, Atlanta, Georgia 30322, USA.
authors: Xiangming
authors: X
authors: Zhang
authors: Wooi-Loon
authors: WL
authors: Ng
authors: Ping
authors: P
authors: Wang
authors: Linlin
authors: L
authors: Tian
authors: Erica
authors: E
authors: Werner
authors: Huichen
authors: H
authors: Wang
authors: Paul
authors: P
authors: Doetsch
authors: Ya
authors: Y
authors: Wang
mesh_terms: D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C441642:SOD3 protein, human; D013482:Superoxide Dismutase