title: Inhibition of cell viability by human IFN-β is mediated by microRNA-431.
abstract: MicroRNAs (miRNAs) are small non-coding RNAs that inhibit gene expression             by cleaving or hindering the translation of target mRNAs. We used microarray-based             comparative transcriptome analysis to identify changes in miRNA expression and             function between a human cell line, RSa, which is highly sensitive to HuIFN-β-mediated             inhibition of cell viability, and its variant, the F-IFr cell line, which is relatively             resistant to the cytokine. miR-431 expression was significantly higher in RSa             cells compared with F-IFr cells. The addition of HuIFN-β to RSa cultures reduced             cell viability, down-regulated expression of IGF1R and IRS2 (putative miR-431             target genes), and inhibited the PI3K-Akt and MAPK pathways. The survival of F-IFr             cells was not reduced by HuIFN-β, but transient transfection with miR-431 precursors             significantly decreased viability and concomitantly down-regulated IGF1R and IRS2             expression. In addition, the MAPK pathway, but not the PI3K-Akt pathway, was suppressed             in F-IFr cells. Based on these results, we propose that, in RSa cells, HuIFN-β-induced             miR-431 expression may down-regulate IGF1R and IRS2 expression, and consequently             inhibit cell proliferation by suppressing the MAPK pathway.
authors.affiliation: Department of Environmental Biochemistry, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba 260-8670, Japan. take64@faculty.chiba-u.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tanaka
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sugaya
authors.forename: Kazuko
authors.initials: K
authors.lastname: Kita
authors.forename: Makoto
authors.initials: M
authors.lastname: Arai
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kanda
authors.forename: Katsunori
authors.initials: K
authors.lastname: Fujii
authors.forename: Fumio
authors.initials: F
authors.lastname: Imazeki
authors.forename: Katsuo
authors.initials: K
authors.lastname: Sugita
authors.forename: Osamu
authors.initials: O
authors.lastname: Yokosuka
authors.forename: Nobuo
authors.initials: N
authors.lastname: Suzuki
mesh_terms: D002461:Cell Line, Transformed; D049109:Cell Proliferation; D002470:Cell Survival; D015536:Down-Regulation; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D016899:Interferon-beta / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D035683:MicroRNAs / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation
chemical_list: C526297:IRS2 protein, human; D055504:Insulin Receptor Substrate Proteins; C573122:MIRN431 microRNA, human; D035683:MicroRNAs; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D016899:Interferon-beta; D058539:Phosphatidylinositol 3-Kinase; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt