Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Specific Expression of Interferon-γ Induced by Synergistic Activation Mediator-Derived Systems Activates Innate Immunity and Inhibits Tumorigenesis

  • Liu, Shuai (School of Basic Medical Sciences, Wuhan University) ;
  • Yu, Xiao (Institute for Infectious Disease Control and Prevention, Hubei Provincial Center for Disease Control and Prevention) ;
  • Wang, Qiankun (School of Basic Medical Sciences, Wuhan University) ;
  • Liu, Zhepeng (School of Basic Medical Sciences, Wuhan University) ;
  • Xiao, Qiaoqiao (School of Basic Medical Sciences, Wuhan University) ;
  • Hou, Panpan (College of Life Sciences, Wuhan University) ;
  • Hu, Ying (College of Life Sciences, Wuhan University) ;
  • Hou, Wei (School of Basic Medical Sciences, Wuhan University) ;
  • Yang, Zhanqiu (School of Basic Medical Sciences, Wuhan University) ;
  • Guo, Deyin (School of Basic Medical Sciences, Wuhan University) ;
  • Chen, Shuliang (School of Basic Medical Sciences, Wuhan University)
  • Received : 2017.05.31
  • Accepted : 2017.08.23
  • Published : 2017.10.28
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Abstract

The synergistic activation mediator (SAM) system can robustly activate endogenous gene expression by a single-guide RNA. This transcriptional modulation has been shown to enhance gene promoter activity and leads to epigenetic changes. Human $interferon-{\gamma}$ is a common natural glycoprotein involved in antiviral effects and inhibition of cancer cell growth. Large quantities of high-purity $interferon-{\gamma}$ are important for medical research and clinical therapy. To investigate the possibility of employing the SAM system to enhance endogenous human $interferon-{\gamma}$ with normal function in innate immunity, we designed 10 single-guide RNAs that target 200 bp upstream of the transcription start sites of the $interferon-{\gamma}$ genome, which could significantly activate the $interferon-{\gamma}$ promoter reporter. We confirmed that the system can effectively and highly activate $interferon-{\gamma}$ expression in several humanized cell lines. Moreover, we found that the $interferon-{\gamma}$ induced by the SAM system could inhibit tumorigenesis. Taken together, our results reveal that the SAM system can modulate epigenetic traits of non-immune cells through activating $interferon-{\gamma}$ expression and triggering JAK-STAT signaling pathways. Thus, this strategy could offer a novel approach to inhibit tumorigenesis without using exogenous $interferon-{\gamma}$.

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References

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