microRNA-101 Provides a Molecular Connection between Pathogenic Inflammation and Lung Tumorigenesis by Regulating Lin28B

Chronic inflammation and infection have been established as key promoting factors of tumorigenesis. Epidemiological data have recognized that chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis, tobacco smoke, air pollutant, pulmonary infections and occupational dust are associated with non-small cell lung cancer (NSCLC), suggesting that chronic inflammation plays important roles in the pathogenesis of NSCLC. Moreover, multiple lines of evidence have confirmed the role of inflammation in the pathogenesis of NSCLC, but the molecular connections between inflammation and NSCLC have remained largely elusive.

WANG Lin, ZHANG Lingfei and their colleagues, under the supervision of Dr. LIU Mofang, studied the pathogenic mechanisms underlying pro-tumorigenic inflammation signaling in NSCLC cells. They found that pro-inflammatory cytokine IL-1β is dramatically elevated in the serum of patients with NSCLC, and that IL-1β promoted the proliferation and migration of NSCLC cells.

Intriguingly, down-regulation of miR-101, a microRNA with an established role in tumor suppression, is critical for the tumor-promoting effect of IL-1 in NSCLC cells. Mechanistically, IL-1β acted through the COX-2/HIF-1α pathway to repress expression of miR-101. Lin28B, an oncogenic RNA-binding protein with pleiotropic roles in cancer including stem-like cell function, 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, COX-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, these findings defined an IL-1β/miR-101/Lin28B pathway as a novel regulatory axis of pathogenic inflammatory signaling in NSCLC.

This work entitled “IL-1β-mediated repression of microRNA-101 is crucial for inflammation-promoted lung tumorigenesis” was published online in Cancer Research on June 23, 2014. This work was collaborated with Drs. LOU Jiatao and LI Dangsheng.

This study was supported by the grants from the Chinese Academy of Sciences, the Ministry of Science and Technology, National Natural Science Foundation of China, and the Science and Technology Commission of Shanghai Municipality.

AUTHOR CONTACT:
LIU Mofang
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences Shanghai 200031, China
Phone: 86-21-54921146
E-mail: mfliu@sibcb.ac.cn

A model of miR-101 as a key regulatory node linking inflammation to lung tumorigenesis. (Image provided by Dr. LIU Mofang`s group)