Downregulation of microRNA-431 by human interferon-β inhibits viability of medulloblastoma and glioblastoma cells via upregulation of SOCS6
Downregulation of microRNA-431 by human interferon-β inhibits viability of medulloblastoma and glioblastoma cells via upregulation of SOCS6
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DOI：
10.3892/ijo.2014.2317
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发表时间：
2014-05-01
影响因子：
5.2
通讯作者：
Yokosuka, Osamu
中科院分区：
文献类型：
--
作者：
Tanaka, Takeshi;Arai, Makoto;Yokosuka, Osamu
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-beta (HuIFN-beta). We aimed to demonstrate an antineoplastic effect of HuIFN-beta via miR-431 expression against medulloblastoma and glioblastoma, because HuIFN-beta is frequently used in adjuvant therapy of these tumors. Addition of HuIFN-beta 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-beta 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-beta decreases miR-431 expression and upregulates SOCS6 expression, and consequently inhibit cell proliferation by suppressing the JAK-STAT signaling pathway.
