DOI: 10.1101/518886Jan 21, 2019Paper

A sustained small increase in NOD1 expression promotes ligand-independent oncogenic activity

BioRxiv : the Preprint Server for Biology
Leah M. RommereimNaeha Subramanian


Small genetically-determined differences in transcription (eQTLs) are implicated in complex disease but the mechanisms by which small changes in gene expression impact complex disease are unknown. Here we show that a persistent small increase in expression of the innate sensor NOD1 precipitates large cancer-promoting changes in cell state. A ~1.2-1.4 fold increase in NOD1 protein concentration by loss of miR-15b/16 regulation sensitizes cells to ligand-induced inflammation, with an additional slight increase leading to ligand-independent NOD1 activation that is linked to poor prognosis in gastric cancer. Our data show that tight expression regulation of NOD1 prevents this sensor from exceeding a physiological switching checkpoint that promotes persistent inflammation and oncogene expression and reveal the impact of a single small quantitative change in cell state on cancer.

Related Concepts

Malignant Neoplasms
Gene Expression
Malignant Neoplasm of Stomach
Transcription, Genetic
Protein Activation
Cell Cycle Checkpoints
Protein Expression

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