title: NF-kB-regulated exosomal miR-155 promotes the inflammation associated with arsenite carcinogenesis.
abstract: In the cancer microenvironment, extracellular communication allows various types of cells to coordinate and execute biological functions. Emerging evidence indicates that exosomes, as mediators of cell communication, are involved in tumor progression. Little is known, however, about the mechanism by which exosomal miRNAs regulate inflammatory infiltration in arsenite-induced liver cancer. The present research aimed to determine if miRNAs secreted from arsenite-transformed human hepatic epithelial (L-02) cells are transferred into normal L-02 and THLE-3 cells, which are functionally active in the recipient cells. The results show that the exosomes from arsenite-transformed L-02 cells enhance miR-155 expression and the pro-inflammatory properties of normal L-02 and THLE-3 cells. Transformed cells transfer miR-155 into normal L-02 cells via exosomes. The inhibition of NF-κB by siRNA and inhibitor, which reduces miR-155 levels in exosomes derived from transformed L-02 cells, blocks inflammation. Arsenite-transformed cells secrete exosomes to enhance inflammation, but the inhibition of the synthesis of exosomes fails to stimulate inflammation. miR-155 is involved in exosome-mediated intercellular communication between neoplastic and normal liver cells. In addition, miR-155, IL-6, and IL-8 were over-expressed in the serum of arsenite exposure group. And there was a positive correlation between miR-155 and IL-6 or IL-8 levels. Further, exosomal miR-155 was up-regulated in the serum of arsenite exposure group. Thus, these results show that exosomes derived from transformed L-02 cells transfer miR-155 to surrounding cells, which induces pro-inflammatory activity of normal liver cells. The findings support the concept that exosomal miRNAs are involved in cell-cell communication during carcinogenesis induced by environmental chemicals.
authors.affiliation: Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China; The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.affiliation: Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China; The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Luo
authors.affiliation: Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China; The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China.
authors.forename: Xinlu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China; The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China.
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.affiliation: Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China; The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.affiliation: Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China; The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China.
authors.forename: Qianlei
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China; The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China.
authors.forename: Junchao
authors.initials: J
authors.lastname: Xue
authors.affiliation: Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China; The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China.
authors.forename: Le
authors.initials: L
authors.lastname: Shi
authors.affiliation: The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guiyang Medical University, Guiyang, 550025, Guizhou, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guiyang Medical University, Guiyang, 550025, Guizhou, People's Republic of China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China; The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China. Electronic address: drqzliu@hotmail.com.
authors.forename: Qizhan
authors.initials: Q
authors.lastname: Liu
mesh_terms: D018053:Arsenites / Q000009:adverse effects*; D063646:Carcinogenesis / Q000378:metabolism; D055354:Exosomes / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism*; D014162:Transfection
chemical_list: D018053:Arsenites; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; C015001:arsenite
keywords: Arsenite; Exosomes; Inflammation; miRNA