title: A genotoxic stress-responsive miRNA, miR-574-3p, delays cell growth by suppressing the enhancer of rudimentary homolog gene in vitro.
abstract: MicroRNA (miRNA) is a type of non-coding RNA that regulates the expression of its target genes by interacting with the complementary sequence of the target mRNA molecules. Recent evidence has shown that genotoxic stress induces miRNA expression, but the target genes involved and role in cellular responses remain unclear. We examined the role of miRNA in the cellular response to X-ray irradiation by studying the expression profiles of radio-responsive miRNAs and their target genes in cultured human cell lines. We found that expression of miR-574-3p was induced in the lung cancer cell line A549 by X-ray irradiation. Overexpression of miR-574-3p caused delayed growth in A549 cells. A predicted target site was detected in the 3'-untranslated region of the enhancer of the rudimentary homolog (ERH) gene, and transfected cells showed an interaction between the luciferase reporter containing the target sequences and miR-574-3p. Overexpression of miR-574-3p suppressed ERH protein production and delayed cell growth. This delay was confirmed by knockdown of ERH expression. Our study suggests that miR-574-3p may contribute to the regulation of the cell cycle in response to X-ray irradiation via suppression of ERH protein production.
authors.affiliation: Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute for Radiological Sciences, Anagawa 4-9-1, Inage, Chiba 263-8555, Japan. k_ishi@nirs.go.jp.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Ishikawa
authors.affiliation: Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute for Radiological Sciences, Anagawa 4-9-1, Inage, Chiba 263-8555, Japan. a_ishi@nirs.go.jp.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Ishikawa
authors.affiliation: Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute for Radiological Sciences, Anagawa 4-9-1, Inage, Chiba 263-8555, Japan. y_otsuka@nirs.go.jp.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Shoji
authors.affiliation: Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute for Radiological Sciences, Anagawa 4-9-1, Inage, Chiba 263-8555, Japan. imait@nirs.go.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Imai
mesh_terms: D020413:3' Untranslated Regions; D059447:Cell Cycle Checkpoints; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D004249:DNA Damage / Q000528:radiation effects; D015536:Down-Regulation; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014965:X-Rays
chemical_list: D020413:3' Untranslated Regions; D018797:Cell Cycle Proteins; C484495:ERH protein, human; C558811:MIRN574 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D014157:Transcription Factors