title: Downregulation of microRNA-431 by human interferon-β inhibits viability of medulloblastoma and glioblastoma cells via upregulation of SOCS6.
abstract: miRNAs are small non-coding RNAs that inhibit gene expression by cleaving or hindering the translation of target mRNAs. In this study, we focused on miR-431, which mediated inhibition of cell viability by human interferon-β (HuIFN-β). We aimed to demonstrate an antineoplastic effect of HuIFN-β via miR-431 expression against medulloblastoma and glioblastoma, because HuIFN-β is frequently used in adjuvant therapy of these tumors. Addition of HuIFN-β to medulloblastoma and glioblastoma cells reduced viability, significantly decreased miR-431 expression, upregulated expression of SOCS6 (putative miR-431 target genes) and inhibited Janus kinase (JAK) 1 and signal transducer and activator of transcription (STAT) 2. The mitogen-activated protein kinase (MAPK) pathway, but not the phosphoinositide 3-kinase (PI3K)-Akt pathway, was downregulated in medulloblastoma cells, whereas the PI3K-Akt pathway, but not the MAPK pathway, was downregulated in glioblastoma cells. Addition of HuIFN-β and transient transfection with miR-431 to medulloblastoma and glioblastoma cells did not reduce viability, downregulated expression of SOCS6, and concomitantly activated the JAK1 and STAT2. We propose that, in medulloblastoma and glioblastoma cells, HuIFN-β decreases miR-431 expression and upregulates SOCS6 expression, and consequently inhibit cell proliferation by suppressing the JAK-STAT signaling pathway.
authors.affiliation: Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Arai
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Xia
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sugaya
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kanda
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Fujii
authors.affiliation: Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Kita
authors.affiliation: Faculty of Education, Chiba University, Chiba 263-8522, Japan.
authors.forename: Katsuo
authors.initials: K
authors.lastname: Sugita
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Imazeki
authors.affiliation: Department of Molecular Genetics, Kitasato University Graduate School of Medical Sciences, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miyashita
authors.affiliation: Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kaneda
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Yokosuka
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D035683:MicroRNAs / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C573122:MIRN431 microRNA, human; D035683:MicroRNAs; C473085:SOCS6 protein, human; D050826:Suppressor of Cytokine Signaling Proteins; D016899:Interferon-beta