Clariom S Microarray Expression Data from Mouse Colonic Lesion and Healthy Tissue following AOM/DSS Chemical Induction of Colitis-associated Colorectal Cancer to Assess NF-κB Mediated Intestinal Epithelial Cell Regeneration. Clariom S Microarray Expression Data from Mouse Colonic Lesion and Healthy Tissue following AOM/DSS Chemical Induction of Colitis-associated Colorectal Cancer to Assess NF-κB Mediated Intestinal Epithelial Cell Regeneration

This study sought to evaluate the diffferential gene expression following the conditional knockout of either the canonical (p65) or non-canonical (NIK) NF-κB signaling pathway in myeloid (LysMCre) or intestinal epithelial (VillinCre) cell deletions in a murine model. Genetic susceptibility to colitis-associated colorectal cancer via the chemical induction of AOM/DSS was evaluated on colonic lesion (LT) and healthy tissue (HT) using microarray to assess implicated genes/pathways downstream of NF-kappaB. Abstract from associated publication: Dysregulation of intestinal epithelial cell proliferation is a critical feature in the development of colorectal cancer. This malignancy is typically driven by loss of stem cell regulation in the crypts. Here, we show that NF-κB-inducing kinase (NIK) attenuates colorectal cancer through the regulation of intestinal epithelial cell regeneration and differentiation mediated by noncanonical NF-κB signaling. We observed increased tumor burden in mice lacking NIK either systemically or specifically in intestinal epithelial cells in a model of inflammation-induced tumorigenesis in the colon. Mechanistic studies using crypts and organoids revealed that loss of NIK results in the accumulation of mature, non-dividing colonic epithelial cells, which are more susceptible to mutations and eventual transformation. These findings are consistent with our observations in human colorectal cancer patients revealing a significant decrease in NIK and noncanonical NF-κB signaling. Our work extends previous findings for NIK in attenuating sepsis and gastrointestinal inflammation and defines a critical role for this kinase in colorectal cancer. Overall design: RNA extractions were collected from each lesion tissue (LT) and healthy tissue (HT) sample using a Qiagen AllPrep Kit. Groups include Nikfl/fl x VillinCre mice (n=3), Nikfl/fl mice (n=3), RelAfl/fl x LysMCre mice (n=3), RelAfl/fl mice (n=3). 4 mouse strains (groups) x3 replicates of LT and HT was collected and assessed for each group totaling n=24. 1 MRSL, provided by the manufacturer, was included.

本研究旨在评估小鼠模型中，分别在髓系细胞（LysMCre）或肠上皮细胞（VillinCre）中条件性敲除经典（p65）或非经典核因子κB（NF-κB）信号通路后的基因表达差异。本研究通过化学诱导氧化偶氮甲烷/葡聚糖硫酸钠（AOM/DSS）构建结肠炎相关结直肠癌模型，利用基因芯片检测结肠病变组织（LT）与健康组织（HT）中核因子κB下游的相关基因及通路，以评估该模型下的结直肠癌遗传易感性。
相关研究论文摘要如下：肠上皮细胞增殖失调是结直肠癌发生的关键特征之一，该恶性肿瘤通常由隐窝干细胞调控失衡所驱动。本研究发现，核因子κB诱导激酶（NIK）可通过介导非经典核因子κB信号通路调控肠上皮细胞再生与分化，从而抑制结直肠癌发生。在结肠炎症诱导的肿瘤发生模型中，全身或肠上皮细胞特异性敲除NIK的小鼠肿瘤负荷显著升高。利用隐窝与类器官进行的机制研究显示，NIK缺失会导致成熟的非增殖性结肠上皮细胞聚集，这类细胞更易发生突变并最终发生恶性转化。该结果与结直肠癌患者样本中的观测结果一致：患者体内NIK及非经典核因子κB信号通路的活性显著降低。本研究拓展了此前关于NIK在抑制脓毒症与胃肠道炎症中的作用的发现，并明确了该激酶在结直肠癌发生中的关键功能。
实验整体设计：采用Qiagen AllPrep试剂盒提取所有结肠病变组织（LT）与健康组织（HT）样本的RNA。实验分组如下：Nikfl/fl x VillinCre小鼠（n=3）、Nikfl/fl小鼠（n=3）、RelAfl/fl x LysMCre小鼠（n=3）及RelAfl/fl小鼠（n=3）。每组分别收集3份LT与HT生物学重复样本，4个实验组共计24份样本。实验中加入了1份由试剂盒生产商提供的MRSL作为参照样本。