Downregulation of microRNA-431 by human interferon-β inhibits viability of medulloblastoma and glioblastoma cells via upregulation of SOCS6

Tanaka,Takeshi; Arai,Makoto; Jiang,Xia; Sugaya,Shigeru; Kanda,Tatsuo; Fujii,Katsunori; Kita,Kazuko; Sugita,Katsuo; Imazeki,Fumio; Miyashita,Toshiyuki; Kaneda,Atsushi; Yokosuka,Osamu

doi:10.3892/ijo.2014.2317

Downregulation of microRNA-431 by human interferon-β inhibits viability of medulloblastoma and glioblastoma cells via upregulation of SOCS6

Authors:
- Takeshi Tanaka
- Makoto Arai
- Xia Jiang
- Shigeru Sugaya
- Tatsuo Kanda
- Katsunori Fujii
- Kazuko Kita
- Katsuo Sugita
- Fumio Imazeki
- Toshiyuki Miyashita
- Atsushi Kaneda
- Osamu Yokosuka
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Affiliations: Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan, Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan, Department of Pediatrics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan, Faculty of Education, Chiba University, Chiba 263-8522, Japan, Department of Molecular Genetics, Kitasato University Graduate School of Medical Sciences, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan
Published online on: February 28, 2014 https://doi.org/10.3892/ijo.2014.2317
Pages: 1685-1690

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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.

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