title: miR-127 promotes EMT and stem-like traits in lung cancer through a feed-forward regulatory loop.
abstract: The coordination between cellular differentiation and the mesenchymal/stem transition is essential for both embryo development and neoplasia, suggesting a mechanistic link between these two major processes. In this work we show that miR-127, an embryo-expressing lung miRNA, was prominently induced in lung adenocarcinoma and correlated with poor prognosis. Elevated miR-127 level drove a pronounced shift from the epithelial to the mesenchymal phenotype in cancer cells, and this shift was associated with their acquisition of stem-like traits, increased resistance to the epidermal growth factor receptor inhibitor and tumor-propagating potential. In contrast, antagonizing miR-127 markedly reversed this malignant transition, compromised the stem-like properties and the in vivo tumorigenic capability of cancer cells. Importantly, a regulatory loop involving the inflammatory signals NF-κB, miR-127 and tumor necrosis factor alpha-induced protein 3 was uncovered as a self-reinforcing circuitry that ensured an aggressive transition in lung cancer. Thus, this work identifies a novel molecular mechanism linking stemness, malignancy and inflammation, opening a new avenue for cancer treatment.
authors.affiliation: Department of Immunology, School of Basic Medical Science, Nanjing University of Chinese Medicine, Nanjing, China.|Department of Basic Medical Science, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, China.
authors.forename: L
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Basic Medical Science, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Basic Medical Science, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Basic Medical Science, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, China.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Basic Medical Science, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, China.
authors.forename: N
authors.initials: N
authors.lastname: Zhuang
authors.affiliation: Department of Basic Medical Science, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, China.
authors.forename: B
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Song
authors.affiliation: Department of Oncology, Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, Zhejiang, China.
authors.forename: G
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Oncology, Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, Zhejiang, China.
authors.forename: C
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Basic Medical Science, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, China.|Department of Molecular and Translational Science, Monash University, Melbourne, VIC, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Medical Oncology, Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Immunology, School of Basic Medical Science, Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Immunology, School of Basic Medical Science, Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Gao
mesh_terms: D020413:3' Untranslated Regions; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000970:Antineoplastic Agents / Q000494:pharmacology; D002465:Cell Movement / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D000077156:Gefitinib; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D011799:Quinazolines / Q000494:pharmacology; D034622:RNA Interference; D015398:Signal Transduction; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3 / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; C547276:MIRN127 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D011799:Quinazolines; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D000077156:Gefitinib