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

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-1β is dramatically elevated in the serum of patients with non–small cell lung cancer (NSCLC). In vitro studies showed that IL-1β promoted the proliferation and migration of NSCLC cells. Mechanistically, IL-1β acted through the COX2–HIF1α pathway to repress the expression of microRNA-101 (miR-101), a microRNA with an established role in tumor suppression. Lin28B was identified as critical effector target of miR-101 with its repression of Lin28B, a critical aspect of tumor suppression. Overall, IL-1β upregulated Lin28B by downregulating miR-101. Interestingly, cyclooxygenase-2 inhibition by aspirin or celecoxib abrogated IL-1β-mediated repression of miR-101 and IL-1β-mediated activation of Lin28B along with their stimulatory effects on NSCLC cell proliferation and migration. Together, our findings defined an IL-1β–miR-101–Lin28B pathway as a novel regulatory axis of pathogenic inflammatory signaling in NSCLC. Cancer Res; 74(17); 4720–30. ©2014 AACR.