Specific Expression of Interferon-γ Induced by Synergistic Activation Mediator-Derived Systems Activates Innate Immunity and Inhibits Tumorigenesis
자연과학 > 생물
( Shuai Liu ) , ( Xiao Yu ) , ( Qiankun Wang ) , ( Zhepeng Liu ) , ( Qiaoqiao Xiao ) , ( Panpan Hou ) , ( Ying Hu ) , ( Wei Hou ) , ( Zhanqiu Yang ) , ( Deyin Guo ) , ( Shuliang Chen )
한국미생물생명공학회(구 한국산업미생물학회)
Journal of Microbiology and Biotechnology 2017년, 제27권 제10호, 1855~1866페이지(총12페이지)
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    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-γ is a common natural glycoprotein involved in antiviral effects and inhibition of cancer cell growth. Large quantities of high-purity interferon-γ are important for medical research and clinical therapy. To investigate the possibility of employing the SAM system to enhance endogenous human interferon-γ 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-γ genome, which could significantly activate the interferon-γ promoter reporter. We confirmed that the system can effectively and highly activate interferon-γ expression in several humanized cell lines. Moreover, we found that the interferon-γ 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-γ expression and triggering JAK-STAT signaling pathways. Thus, this strategy could offer a novel approach to inhibit tumorigenesis without using exogenous interferon-γ.
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