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A modest change in regulation of NOD1 expression has a major impact on inflammation and gastric cancer

ABSTRACT: Altered protein dosage by defects in single genes leads to haploinsufficiencies and monogenic disorders, but the impact of small changes in gene expression on multifactorial disease is unknown. Here we show that a persistent small increase in expression of NOD1, a key innate sensor of bacterial infection, precipitates a large physiological effect with dramatically altered cellular function associated with carcinogenesis. Inhibition of miR-15b and miR-16 microRNA function leads to a ~1.2-1.4 fold increase in NOD1 protein concentration, with even slightly greater increases leading to ligand-independent, switch-like NOD1 activation. miRNA regulation of NOD1 is impaired in gastric cancer with a small increase being associated with greater early disease mortality. Overall, our data show that tight control of NOD1 expression by miRNA prevents this sensor from exceeding a physiological switching checkpoint that promotes persistent inflammation and lethal cancer progression, and reveal the impact of a single and modest cellular alteration on cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE99550 | GEO | 2020/10/01

REPOSITORIES: GEO

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