title: MicroRNA-33b inhibits lung adenocarcinoma cell growth, invasion, and epithelial-mesenchymal transition by suppressing Wnt/β-catenin/ZEB1 signaling.
abstract: Altered expression of microRNA (miRNA) is associated with lung carcinogenesis and metastasis. Our previous study of lung cancer miRNAs using the gene chip assay demonstrated altered miR-33b expression in lung adenocarcinoma. The present study further investigated miR-33b expression, function, and gene regulation in lung cancer cells in vitro and in nude mouse xenografts. Our data showed that the level of miR-33b expression was dramatically decreased in lung adenocarcinoma cell lines and tissues and that the reduced miR-33b expression was associated with tumor lymph node metastasis. Furthermore, restoration of miR-33b expression inhibited lung adenocarcinoma cell proliferation, migration, and invasion and tumor cell epithelial-mesenchymal transition (EMT) in vitro. Luciferase assay revealed that miR-33b bound to ZEB1 3'-UTR region and inhibited ZEB1 expression, while expression of ZEB1 mRNA and miR-33b was inversely associated with lung adenocarcinoma cell lines and tissues. Subsequently, we found that miR-33b suppressed the activity of WNT/β-catenin signaling in lung adenocarcinoma cells and in turn suppressed tumor cell growth and EMT in vitro and in vivo nude mouse xenografts. In conclusion, the present study provided novel insight into the molecular mechanism of lung adenocarcinoma progression. MicroRNA-33b should be further investigated as a potential therapeutic target in human lung adenocarcinoma.
authors.affiliation: Department of Respiratory Medicine, Xiangya Hospital, The Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Qu
authors.affiliation: Department of Respiratory Medicine, Xiangya Hospital, The Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, Xiangya Hospital, The Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: An
authors.affiliation: Department of Respiratory Medicine, Xiangya Hospital, The Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Bingrong
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Department of Respiratory Medicine, Xiangya Hospital, The Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhong
authors.affiliation: Department of Respiratory Medicine, Xiangya Hospital, The Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Qihua
authors.initials: Q
authors.lastname: Gu
authors.affiliation: Department of Respiratory Medicine, Xiangya Hospital, The Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Liming
authors.initials: L
authors.lastname: Cao
authors.affiliation: Department of Respiratory Medicine, Xiangya Hospital, The Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Huaping
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Respiratory Medicine, Xiangya Hospital, The Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Chengping
authors.initials: C
authors.lastname: Hu
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D064593:Heterografts; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D016133:Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000235:genetics*; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D018398:Homeodomain Proteins; C550416:MIRN33a microRNA, human; D035683:MicroRNAs; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1