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

Abstract

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
Inflammation
Ligands
Malignant Neoplasm of Stomach
Oncogenes
Transcription, Genetic
Protein Activation
Cell Cycle Checkpoints
Protein Expression

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