Wei Liu1, Congwen Zhuang1, Tengfei Huang1, Shengsheng Yang1, Meiqing Zhang1, Baoquan Lin2, Yi Jiang3. 1. Department of Respiratory and Critical Care Medicine, The 900th Hospital of Joint Logistic Support Force, Fuzhou, Fujian, China. 2. Department of Thoracic Surgery, The 900th Hospital of Joint Logistic Support Force, Fuzhou, Fujian, China. 3. Department of Hepatobiliary Surgery, The 900th Hospital of Joint Logistic Support Force, Fuzhou, Fujian, China.
Abstract
OBJECTIVE: This study aimed to identify critical genes involved in the tumor biology of lung cancer via datamining of The Cancer Genome Atlas (TCGA) with special focus on gene copy number variation. METHODS: Genomic deletion and amplification were analyzed with cBioportal online tools. Relative expression of Cyclin Dependent Kinase Inhibitor 2A (CDKN2A) was analyzed by both real-time polymerase chain reaction (PCR) and Western blot. The abundance of methylthioadenosine phosphorylase (MTAP) and epithelial-mesenchymal transition markers were analyzed by real-time PCR. Cell proliferation was determined by cell counting kit-8 method and cell viability was measured with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The cell migration and invasion were measured with transwell chamber assay, and migrative capacity was further evaluated by wound healing assay. RESULTS: We found the frequent loss of CDKN2A was associated with its downregulation in lung cancer, and siRNA-mediated CDNKN2A knockdown significantly stimulated cell proliferation, invasion, and migration. Mechanistically, we unraveled that MTAP, which was positively correlated with CDKN2A, predominantly mediated the antitumoral function of CDKN2A in lung cancer. CONCLUSION: Our study consolidated the involvement of CDKN2A-MTAP signaling in the context of lung cancer.
OBJECTIVE: This study aimed to identify critical genes involved in the tumor biology of lung cancer via datamining of The Cancer Genome Atlas (TCGA) with special focus on gene copy number variation. METHODS: Genomic deletion and amplification were analyzed with cBioportal online tools. Relative expression of Cyclin Dependent Kinase Inhibitor 2A (CDKN2A) was analyzed by both real-time polymerase chain reaction (PCR) and Western blot. The abundance of methylthioadenosine phosphorylase (MTAP) and epithelial-mesenchymal transition markers were analyzed by real-time PCR. Cell proliferation was determined by cell counting kit-8 method and cell viability was measured with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The cell migration and invasion were measured with transwell chamber assay, and migrative capacity was further evaluated by wound healing assay. RESULTS: We found the frequent loss of CDKN2A was associated with its downregulation in lung cancer, and siRNA-mediated CDNKN2A knockdown significantly stimulated cell proliferation, invasion, and migration. Mechanistically, we unraveled that MTAP, which was positively correlated with CDKN2A, predominantly mediated the antitumoral function of CDKN2A in lung cancer. CONCLUSION: Our study consolidated the involvement of CDKN2A-MTAP signaling in the context of lung cancer.
Authors: Konstantinos J Mavrakis; E Robert McDonald; Michael R Schlabach; Eric Billy; Gregory R Hoffman; Antoine deWeck; David A Ruddy; Kavitha Venkatesan; Jianjun Yu; Gregg McAllister; Mark Stump; Rosalie deBeaumont; Samuel Ho; Yingzi Yue; Yue Liu; Yan Yan-Neale; Guizhi Yang; Fallon Lin; Hong Yin; Hui Gao; D Randal Kipp; Songping Zhao; Joshua T McNamara; Elizabeth R Sprague; Bing Zheng; Ying Lin; Young Shin Cho; Justin Gu; Kenneth Crawford; David Ciccone; Alberto C Vitari; Albert Lai; Vladimir Capka; Kristen Hurov; Jeffery A Porter; John Tallarico; Craig Mickanin; Emma Lees; Raymond Pagliarini; Nicholas Keen; Tobias Schmelzle; Francesco Hofmann; Frank Stegmeier; William R Sellers Journal: Science Date: 2016-02-11 Impact factor: 47.728
Authors: G I Shapiro; C D Edwards; L Kobzik; J Godleski; W Richards; D J Sugarbaker; B J Rollins Journal: Cancer Res Date: 1995-02-01 Impact factor: 12.701