PDF(Pubmed)
Abstract：
Streptococcus gallolyticus sp. gallolyticus (SGG) is a gut pathobiont involved in the development of colorectal cancer (CRC). To decipher SGG contribution in tumor initiation and/or acceleration respectively, a global transcriptome was performed in human normal colonic cells (FHC) and in human tumoral colonic cells (HT29). To identify SGG-specific alterations, we chose the phylogenetically closest relative, Streptococcus gallolyticus subsp. macedonicus (SGM) as control bacterium. We show that SGM, a bacterium generally considered as safe, did not induce any transcriptional changes on the two human colonic cells. The transcriptional reprogramming induced by SGG in normal FHC and tumoral HT29 cells was significantly different, although most of the genes up- and down-regulated were associated with cancer disease. Top up-regulated genes related to cancer were: (i) IL-20, CLK1, SORBS2, ERG1, PIM1, SNORD3A for normal FHC cells and (ii) TSLP, BHLHA15, LAMP3, ZNF27B, KRT17, ATF3 for cancerous HT29 cells. The total number of altered genes were much higher in cancerous than in normal colonic cells (2,090 vs 128 genes being affected, respectively). Gene set enrichment analysis reveals that SGG-induced strong ER- (endoplasmic reticulum) stress and UPR- (unfolded protein response) activation in colonic epithelial cells. Our results suggest that SGG induces a pro-tumoral shift in human colonic cells particularly in transformed cells potentially accelerating tumor development in the colon.
摘要：
溶胆链球菌。胆溶菌(SGG)是一种参与结直肠癌(CRC)发生发展的肠道病变。为了分别破译SGG在肿瘤起始和/或加速中的贡献，在人类正常结肠细胞(FHC)和人类肿瘤结肠细胞(HT29)中进行了全局转录组.为了识别SGG特异性改变，我们选择了系统发育上最接近的亲戚，溶胆链球菌亚种。Macedonicus（SGM）作为对照细菌。我们证明SGM，通常被认为是安全的细菌，在两个人结肠细胞上没有诱导任何转录变化。SGG诱导的正常FHC和肿瘤HT29细胞的转录重编程有显著差异,尽管大多数上调和下调的基因与癌症疾病相关。与癌症相关的最高上调基因是：（i）正常FHC细胞的IL-20，CLK1，SORBS2，ERG1，PIM1，SNORD3A和（ii）TSLP，BHLHA15,LAMP3,ZNF27B,KRT17、ATF3用于癌性HT29细胞。癌变基因的总数远高于正常结肠细胞（2,090个基因与128个基因受影响，分别)。基因集富集分析揭示了SGG诱导的结肠上皮细胞中的强ER-(内质网)应激和UPR-(未折叠蛋白应答)活化。我们的结果表明，SGG在人结肠细胞中特别是在转化细胞中诱导促肿瘤转移，可能加速结肠中的肿瘤发展。
