title: miR-497 and miR-34a retard lung cancer growth by co-inhibiting cyclin E1 (CCNE1).
abstract: Cyclin E1, encoded by the CCNE1 gene, promotes G1/S transition, chromosome instability, and oncogenesis. Here, we show that miR-497 and miR-34a target the 3'-UTR of CCNE1. miR-497 and miR-34a are downregulated in cancer cells and their ectopic expression inhibited cell proliferation and colony formation in vitro, and inhibited tumor growth in a xenograft model. The effect of simultaneous overexpression of miR-497 and miR-34a on the inhibition of cell proliferation, colony formation, and tumor growth, and the downregulation of cyclin E1 was stronger than the effect of each miRNA alone. The synergistic actions of miR-497 and miR-34a partly correlated with cyclin E1 levels. When cells stably expressing CCNE1 were transfected with the Hi-miR-497/34a plasmid, there was no effect on colony formation, compared with that of cells transfected with either Hi-miR497 or Hi-miR34a. These results indicate cyclin E1 is downregulated by both miR-497 and miR-34a, which synergistically retard the growth of human lung cancer cells.
authors.affiliation: State Key Laboratory of Respiratory Disease, Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou, P.R. China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Han
authors.affiliation: Department of Pulmonary Tuberculosis, Guangzhou Chest Hospital, Guangzhou, P.R. China.
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Respiratory Disease, Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou, P.R. China.
authors.forename: Qiaoyuan
authors.initials: Q
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Respiratory Disease, Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou, P.R. China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Respiratory Disease, Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou, P.R. China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Pathology, Guangzhou Medical University, Guangzhou, P.R. China.
authors.forename: Yajie
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Center for Integrative Toxicology, Michigan State University, East Lansing, MI, USA.
authors.forename: Chengfeng
authors.initials: C
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Respiratory Disease, Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou, P.R. China.
authors.forename: Yiguo
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D019927:Cyclin E / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000502:physiology*; D015513:Oncogene Proteins / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C475820:CCNE1 protein, human; D019927:Cyclin E; C522425:MIRN34 microRNA, human; C559640:MIRN497 microRNA, human; D035683:MicroRNAs; D015513:Oncogene Proteins
keywords: CCNE1; lung cancer; miR-34a; miR-497