title: MiR-21 is involved in radiation-induced bystander effects.
abstract: Radiation-induced bystander effects are well-established phenomena, in which DNA damage responses are induced not only in the directly irradiated cells but also in the non-irradiated bystander cells through intercellular signal transmission. Recent studies hint that bystander effects are possibly mediated via small non-coding RNAs, especially microRNAs. Thus, more details about the roles of microRNA in bystander effects are urgently needed to be elucidated. Here we demonstrated that bystander effects were induced in human fetal lung MRC-5 fibroblasts through medium-mediated way by different types of radiation. We identified a set of differentially expressed microRNAs in the cell culture medium after irradiation, among which the up-regulation of miR-21 was further verified with qRT-PCR. In addition, we found significant upregulation of miR-21 in both directly irradiated cells and bystander cells, which was confirmed by the expression of miR-21 precursor and its target genes. Transfection of miR-21 mimics into non-irradiated MRC-5 cells caused bystander-like effects. Taken together, our data reveals that miR-21 is involved in radiation-induced bystander effects. Elucidation of such a miRNA-mediated bystander effect is of utmost importance in understanding the biological processes related to ionizing radiation and cell-to-cell communication.
authors.affiliation: a Department of Space Radiobiology; Key Laboratory of Heavy Ion Radiation Biology and Medicine; Institute of Modern Physics; Chinese Academy of Sciences ; Lanzhou , P.R. China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Xu
authors.forename: Nan
authors.initials: N
authors.lastname: Ding
authors.forename: Hailong
authors.initials: H
authors.lastname: Pei
authors.forename: Wentao
authors.initials: W
authors.lastname: Hu
authors.forename: Wenjun
authors.initials: W
authors.lastname: Wei
authors.forename: Xurui
authors.initials: X
authors.lastname: Zhang
authors.forename: Guangming
authors.initials: G
authors.lastname: Zhou
authors.forename: Jufang
authors.initials: J
authors.lastname: Wang
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D024201:Bystander Effect; D002450:Cell Communication / Q000528:radiation effects; D049109:Cell Proliferation; D002478:Cells, Cultured; D004249:DNA Damage / Q000528:radiation effects; D005333:Fetus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D011839:Radiation, Ionizing; D017382:Reactive Oxygen Species; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000528:radiation effects; D014410:Tumor Stem Cell Assay
chemical_list: C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D017382:Reactive Oxygen Species
keywords: 3′-UTR, 3′-untranslated region; IR, ionizing radiation; RIBE, radiation-induced bystander effects; ROS, reactive oxygen species; TGFβ1, transforming growth factor-beta 1; TNFα, tumor necrosis factor-alpha; bystander effect; medium; miR-21; miR-21, microRNA-21; miRNA, microRNA; microRNA; pre-miR-21, the precursor of miR-21; radiation