title: IL-1β-mediated repression of microRNA-101 is crucial for inflammation-promoted lung tumorigenesis.
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.
authors: 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.
authors: Lin
authors: L
authors: Wang
authors: 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.
authors: Ling-Fei
authors: LF
authors: Zhang
authors: Department of Laboratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors: Jing
authors: J
authors: Wu
authors: Department of Laboratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors: Shu-Jun
authors: SJ
authors: Xu
authors: Department of Laboratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors: Yang-Yang
authors: YY
authors: Xu
authors: Shanghai Information Center for Life Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors: Dangsheng
authors: D
authors: Li
authors: Department of Laboratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. loujiatao@126.com mfliu@sibcb.ac.cn.
authors: Jia-Tao
authors: JT
authors: Lou
authors: 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.
authors: Mo-Fang
authors: MF
authors: Liu
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D053583:Interleukin-1beta; C534072:MIRN101 microRNA, human; D035683:MicroRNAs; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human