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( 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) 2017 Journal of microbiology and biotechnology Vol.27 No.10
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.