System analysis of the regulation of the immune response by CD147 and FOXC1 in cancer cell lines

// Yu-Kui Shang 1, 2, * , Can Li 2, * , Ze-Kun Liu 2, * , Ling-Min Kong 2 , Ding Wei 2 , Jing Xu 2 , Zi-Ling Wang 1 , Huijie Bian 2 and Zhi-Nan Chen 1, 2 1 College of Life Sciences and Bioengineering, Beijing Jiaotong University, Beijing, 100044, China 2 State Key Laboratory of Cancer Biology, Cell Engineering Research Center and Department of Cell Biology, Fourth Military Medical University, Xi'an, 71032, China * These authors contributed equally to this work Correspondence to: Zhi-Nan Chen, email: znchen@fmmu.edu.cn Huijie Bian, email: hjbian@fmmu.edu.cn Keywords: CD147; immune response; FOXC1; gene expression; cancer cell line encyclopedia Received: July 13, 2017      Accepted: December 03, 2017      Published: January 11, 2018 ABSTRACT CD147, encoded by BSG , is a highly glycosylated transmembrane protein that belongs to the immunological superfamily and expressed on the surface of many types of cancer cells. While CD147 is best known as a potent inducer of extracellular matrix metalloproteinases, it can also function as a key mediator of inflammatory and immune responses. To systematically elucidate the function of CD147 in cancer cells, we performed an analysis of genome-wide profiling across the Cancer Cell Line Encyclopedia (CCLE). We showed that CD147 mRNA expression was much higher than that of most other genes in cancer cell lines. CD147 varied widely across these cell lines, with the highest levels in the ovary (COLO704) and stomach (SNU668), intermediate levels in the lung (RERFLCKJ, NCIH596 and NCIH1651) and lowest levels in hematopoietic and lymphoid tissue (UT7, HEL9217, HEL and MHHCALL3) and the kidney (A704 and SLR20). Genome-wide analyses showed that CD147 expression was significantly negatively correlated with immune-related genes. Our findings implicated CD147 as a novel regulator of immune-related genes and suggest its important role as a master regulator of immune-related responses in cancer cell lines. We also found a high correlation between the expression of CD147 and FOXC1, and proved that CD147 was a direct transcriptional target of FOXC1. Our findings demonstrate that FOXC1 is a novel regulator of CD147 and confirms its role as a master regulator of the immune response.