Inflammation-Promoted Lung Tumorigenesis-Mediated Repression of microRNA-101 Is Crucial for β IL-1

Inflammatory stimuli clearly contribute to lung cancer development and progression, but the underlying pathogenic mechanisms are not fully understood. We found that the proinflammatory cytokine IL-1b is dramatically elevated in the serum of patients with non–small cell lung cancer (NSCLC). In vitro studies showed that IL-1b promoted the proliferation and migration of NSCLC cells. Mechanistically, IL-1b acted through the COX2–HIF1a pathway to repress the expression of microRNA-101 (miR-101), a microRNA with an established role in tumor suppression. Lin28Bwas identified as critical effector target ofmiR-101with its repression of Lin28B, a critical aspect of tumor suppression. Overall, IL-1b upregulated Lin28B by downregulating miR-101. Interestingly, cyclooxygenase-2 inhibition by aspirin or celecoxib abrogated IL-1b-mediated repression of miR-101 and IL-1b-mediated activation of Lin28B along with their stimulatory effects on NSCLC cell proliferation and migration. Together, our findings defined an IL-1b–miR-101–Lin28B pathway as a novel regulatory axis of pathogenic inflammatory signaling in NSCLC. Cancer Res; 74(17); 4720–30. 2014 AACR.