title: STAT3-regulated exosomal miR-21 promotes angiogenesis and is involved in neoplastic processes of transformed human bronchial epithelial cells.
abstract: Although microRNA (miRNA) enclosed in exosomes can mediate intercellular communication, the roles of exosomal miRNA and angiogenesis in lung cancer remain unclear. We investigated functions of STAT3-regulated exosomal miR-21 derived from cigarette smoke extract (CSE)-transformed human bronchial epithelial (HBE) cells in the angiogenesis of CSE-induced carcinogenesis. miR-21 levels in serum were higher in smokers than those in non-smokers. The medium from transformed HBE cells promoted miR-21 levels in normal HBE cells and angiogenesis of human umbilical vein endothelial cells (HUVEC). Transformed cells transferred miR-21 into normal HBE cells via exosomes. Knockdown of STAT3 reduced miR-21 levels in exosomes derived from transformed HBE cells, which blocked the angiogenesis. Exosomes derived from transformed HBE cells elevated levels of vascular endothelial growth factor (VEGF) in HBE cells and thereby promoted angiogenesis in HUVEC cells. Inhibition of exosomal miR-21, however, decreased VEGF levels in recipient cells, which blocked exosome-induced angiogenesis. Thus, miR-21 in exosomes leads to STAT3 activation, which increases VEGF levels in recipient cells, a process involved in angiogenesis and malignant transformation of HBE cells. These results, demonstrating the function of exosomal miR-21 from transformed HBE cells, provide a new perspective for intervention strategies to prevent carcinogenesis of lung cancer.
authors.affiliation: Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China; The Key Laboratory of Modern Toxicology, Ministry of Education, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China; The Key Laboratory of Modern Toxicology, Ministry of Education, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Luo
authors.affiliation: Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China; The Key Laboratory of Modern Toxicology, Ministry of Education, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
authors.forename: Bairu
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
authors.forename: Huiqiao
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China; The Key Laboratory of Modern Toxicology, Ministry of Education, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China; The Key Laboratory of Modern Toxicology, Ministry of Education, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
authors.forename: Xinlu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China; The Key Laboratory of Modern Toxicology, Ministry of Education, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
authors.forename: Le
authors.initials: L
authors.lastname: Shi
authors.affiliation: Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China; The Key Laboratory of Modern Toxicology, Ministry of Education, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Lu
authors.affiliation: Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China; The Key Laboratory of Modern Toxicology, Ministry of Education, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
authors.forename: Wenchao
authors.initials: W
authors.lastname: Xu
authors.affiliation: Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China; The Key Laboratory of Modern Toxicology, Ministry of Education, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.affiliation: Institute of Chronic Non-communicable Disease Control, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu 210009, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Institute of Chronic Non-communicable Disease Control, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu 210009, China.
authors.forename: Quanyong
authors.initials: Q
authors.lastname: Xiang
authors.affiliation: Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China; The Key Laboratory of Modern Toxicology, Ministry of Education, Nanjing Medical University, Nanjing, Jiangsu 211166, China. Electronic address: drqzliu@hotmail.com.
authors.forename: Qizhan
authors.initials: Q
authors.lastname: Liu
mesh_terms: D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism*; D055354:Exosomes / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology*; D035683:MicroRNAs / Q000502:physiology*; D018919:Neovascularization, Physiologic; D050796:STAT3 Transcription Factor / Q000502:physiology*; D012906:Smoke / Q000009:adverse effects; D014026:Nicotiana / Q000009:adverse effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D012906:Smoke; D042461:Vascular Endothelial Growth Factor A
keywords: Angiogenesis; Exosomal miRNAs; Intercellular communication; Molecular mechanism