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. 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.