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

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

来源：International Journal of Oncology, 2014, 44(5): 1685-1690.

DOI：10.3892/ijo.2014.2317

• microRNA
• human IFN-beta
• JAK-STAT signaling pathway
• cell viability
• cancer therapy

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.

• 出版日期2014-5