title: MicroRNA-19 triggers epithelial-mesenchymal transition of lung cancer cells accompanied by growth inhibition.
abstract: The miR-19 family (miR-19a and miR-19b-1) are key oncogenic components of the miR-17-92 cluster. Overexpression of miR-19 is strongly associated with cancer invasion and metastasis, and poor prognosis of cancer patients. However, the underlying mechanisms remain largely unknown. In the present study, we found that enforced expression of miR-19 including miR-19a and miR-19b-1 triggered epithelial-mesenchymal transition (EMT) of lung cancer cells A549 and HCC827 as shown by mesenchymal-like morphological conversion, downregulation of epithelial proteins (e.g., E-cadherin, ZO-1 (zona occludens 1), and α-catenin), upregulation of mesenchymal proteins (e.g., vimentin, fibronectin 1, N-cadherin, and snail1), formation of stress fibers, and reduced cell adhesion. In addition, enhanced migration and invasion were observed in the cancer cells A549 and HCC827 undergoing EMT. In contrast, silencing of endogenous miR-19 reversed EMT and reduced the migration and invasion abilities of A549 and HCC827 cells. DNA microarray results revealed significant changes of the expression of genes related to EMT, migration, and metastasis of miR-19-expressing A549 cells. Moreover, siRNA-mediated knockdown of PTEN, a target of miR-19, also resulted in EMT, migration, and invasion of A549 and HCC827 cells, suggesting that PTEN is involved in miR-19-induced EMT, migration and invasion of lung cancer cells. Furthermore, lung cancer cells undergoing EMT induced by miR-19 demonstrated reduced proliferation in vitro and in vivo, and enhanced resistance to apoptosis caused by TNF-α. Taken together, these findings suggest that miR-19 triggers EMT, which has an important role in the invasion and migration of lung cancer cells, accompanied by the reduced proliferation of cells.
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou, China.|Department of Oncology, The First Hospital of Shijiazhuang, Shijiazhuang, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Yang
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou, China.|Department of Oncology, Guangdong No. 2 Provincial People's Hospital, Guangzhou, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Yan
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors.forename: Yu-Juan
authors.initials: YJ
authors.lastname: Qin
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Lin
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors.forename: Rao-Ying
authors.initials: RY
authors.lastname: Xie
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors.forename: Sheng-Chun
authors.initials: SC
authors.lastname: Wang
authors.affiliation: Department of Cardiovascular, Guangdong No. 2 Provincial People's Hospital, Guangzhou, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Jin
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors.forename: Jun-Wen
authors.initials: JW
authors.lastname: Shi
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors.forename: Wen-Tao
authors.initials: WT
authors.lastname: Zhao
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors.forename: Jun-Shuang
authors.initials: JS
authors.lastname: Jia
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors.forename: Hong-Fen
authors.initials: HF
authors.lastname: Shen
authors.affiliation: College of Biotechnology, Southern Medical University, Guangzhou, China.
authors.forename: Jie-Rong
authors.initials: JR
authors.lastname: Ke
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Oncology, Guangdong No. 2 Provincial People's Hospital, Guangzhou, China.
authors.forename: Yi-Qiao
authors.initials: YQ
authors.lastname: Zhao
authors.affiliation: Department of Anatomy, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, China.
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Huang
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors.forename: Kai-Tai
authors.initials: KT
authors.lastname: Yao
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Dan-Juan
authors.initials: DJ
authors.lastname: Li
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou, China.|Institute of Comparative Medicine & Laboratory Animal Center, Southern Medical University, Guangzhou, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Xiao
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000502:physiology*; D005353:Fibronectins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008156:Luciferases; D008175:Lung Neoplasms / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000378:metabolism* / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D034622:RNA Interference; D000071250:Snail Family Transcription Factors; D013778:Tetrazolium Salts; D013844:Thiazoles; D014157:Transcription Factors / Q000378:metabolism; D014410:Tumor Stem Cell Assay; D014746:Vimentin / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000378:metabolism; D051178:alpha Catenin / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C050361:CDH2 protein, human; D015820:Cadherins; C067625:FN1 protein, human; D005353:Fibronectins; C549214:MIRN19A microRNA, human; D035683:MicroRNAs; C000604407:SNAI1 protein, human; C000604429:Snai1 protein, mouse; D000071250:Snail Family Transcription Factors; C569042:TJP1 protein, human; D013778:Tetrazolium Salts; D013844:Thiazoles; D014157:Transcription Factors; D014746:Vimentin; D062826:Zonula Occludens-1 Protein; D051178:alpha Catenin; D008156:Luciferases; C022616:thiazolyl blue