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Cancer Res. 2014 Sep 1;74(17):4720-30. doi: 10.1158/0008-5472.CAN-14-0960. Epub 2014 Jun 23.

IL-1β-mediated repression of microRNA-101 is crucial for inflammation-promoted lung tumorigenesis.

Author information

1
Department of Laboratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. Center for RNA Research, State Key Laboratory of Molecular Biology-University of Chinese Academy of Sciences, Shanghai, China.
2
Center for RNA Research, State Key Laboratory of Molecular Biology-University of Chinese Academy of Sciences, Shanghai, China. Shanghai Key Laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
3
Department of Laboratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
4
Shanghai Information Center for Life Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
5
Department of Laboratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. loujiatao@126.com mfliu@sibcb.ac.cn.
6
Center for RNA Research, State Key Laboratory of Molecular Biology-University of Chinese Academy of Sciences, Shanghai, China. Shanghai Key Laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China. loujiatao@126.com mfliu@sibcb.ac.cn.

Abstract

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.

PMID:
24958470
DOI:
10.1158/0008-5472.CAN-14-0960
[Indexed for MEDLINE]
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