title: Utilization of microRNAs with decreased expression levels in response to X-ray irradiation for fine-tuning radiation-controlled gene regulation.
abstract: We previously developed a promoter that was responsive to radiation by randomly combining cis-elements of transcription factors that are activated in response to radiation in prostate cancer cells. The promoter enhanced the expression of the luciferase gene linked downstream by more than 10-fold 12 h after X-ray irradiation at 10 Gy. However, without radiation, it still significantly drove its expression. To suppress expression while retaining its enhancement in response to radiation, we focused our attention on microRNAs (miRNAs). miRNAs are a group of non-coding RNAs approximately 22 nucleotides long that control gene expression by binding to a target sequence residing on the 3'-untranslated region (3'UTR) of a target gene. We identified 8 miRNAs that were downregulated in response to X-ray irradiation, and inserted artificial target sequences composed of randomly combined complementary sequences into 3 representative miRNAs into the 3'UTR of the luciferase gene. The target sequences suppressed the expression, and released the expression, after X-ray irradiation, as expected. When we combined an artificial target sequence with the radiation-responsive promoter, it resulted in a clear-cut gene regulation of expression that was greater than that induced by the promoter alone.
authors.affiliation: Department of Urology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Morii
authors.forename: Ryohei
authors.initials: R
authors.lastname: Ogawa
authors.forename: Akihiko
authors.initials: A
authors.lastname: Watanabe
authors.forename: Zeng-Guo
authors.initials: ZG
authors.lastname: Cui
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takasaki
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Doi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kondo
authors.forename: Hideki
authors.initials: H
authors.lastname: Fuse
mesh_terms: D045744:Cell Line, Tumor; D015870:Gene Expression / Q000528:radiation effects; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000528:radiation effects*; D017930:Genes, Reporter; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000528:radiation effects; D011471:Prostatic Neoplasms / Q000235:genetics / Q000532:radiotherapy; D020218:Response Elements / Q000528:radiation effects; D014965:X-Rays / Q000009:adverse effects*
chemical_list: D035683:MicroRNAs