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1521-22542222020FebThe journal of gene medicineJ Gene MedGBX2, as a tumor promoter in lung adenocarcinoma, enhances cells viability, invasion and migration by regulating the AKT/ERK signaling pathway.e3147e314710.1002/jgm.3147Increasing evidence shows that gastrulation brain homeobox 2 (GBX2) is involved in multiple cancers. However, whether GBX2 has an effect on the lung adenocarcinoma remains unclear. In the present study, we investigated the functions of GBX2 on lung adenocarcinoma and explored the underlying mechanism.Public data were obtained from the TCGA (https://cancergenome.nih.gov) and Oncomine (http://www.oncomine.org) databases. GBX2 expression and its prognostic value were analyzed by bioinformatics methods. Relative mRNA and protein expression levels of GBX2 in lung adenocarcinoma cell lines were evaluated via a quantitative reverse transcriptase polymerase chain reaction and western blotting. Lung adenocarcinoma cell lines LTEP-a-2 and A549, respectively, were selected for gain and loss function of GBX2 assays. Cell viability was detected by CCK8 and clone formation experiments. Cell invasion and migration were assessed by Transwell assays. The effect of GBX2 on the AKT/extracellular signal regulated kinase (ERK) pathway was tested by western blotting.Compared to adjacent tissues, GBX2 expression was up-regulated in lung adenocarcinoma tissues. High expression of GBX2 led to a poor survival and could be seen as an independent predictor for lung adenocarcinoma patients. Furthermore, down-regulation of GBX2 notably restrained the viability, invasion and migration abilities of A549 cells, whereas up-regulation of GBX2 in LTEP-a-2 cells presented the opposite outcomes. Furthermore, western blot indicated that down-regulation of GBX2 decreases the protein levels of phosphorylated (p)-AKT and p-ERK in A549 cells, whereas up-regulation of GBX2 shows the opposite effects in LTEP-a-2 cells.The results of present study indicate that GBX2 acts a cancer-promoting role to accelerate cell proliferation, invasion and migration partly by modulation of the AKT/ERK pathway in lung adenocarcinoma.© 2019 John Wiley & Sons, Ltd.WangYuanchunYDepartment of Oncology, The Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine, Xianyang, Shaanxi, China.HuiJianpingJDepartment of Gastroenterology, The Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine, Xianyang, Shaanxi, China.LiRentingRDepartment of Oncology, The Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine, Xianyang, Shaanxi, China.FuQiaoqiaoQCollege of Acumox and Tuina, Shaanxi University of Traditional Chinese Medicine, Xi'an, Shaanxi, China.YangPuPCollege of Acumox and Tuina, Shaanxi University of Traditional Chinese Medicine, Xi'an, Shaanxi, China.XiaoYingchunYCollege of Acumox and Tuina, Shaanxi University of Traditional Chinese Medicine, Xi'an, Shaanxi, China.HuiJianrongJ0000-0002-4924-8360College of Acumox and Tuina, Shaanxi University of Traditional Chinese Medicine, Xi'an, Shaanxi, China.engJournal ArticleResearch Support, Non-U.S. Gov't20191220
EnglandJ Gene Med98157641099-498X0GBX2 protein, human0Homeodomain ProteinsEC 2.7.11.1Proto-Oncogene Proteins c-aktEC 2.7.11.24Extracellular Signal-Regulated MAP KinasesIMA549 CellsAdenocarcinoma of LunggeneticspathologyCell Line, TumorCell MovementCell ProliferationCell SurvivalExtracellular Signal-Regulated MAP KinasesmetabolismFemaleGene Expression Regulation, NeoplasticGene Knockdown TechniquesHomeodomain ProteinsgeneticsmetabolismHumansLung NeoplasmsgeneticspathologyMAP Kinase Signaling SystemMaleMiddle AgedNeoplasm InvasivenessPrognosisProto-Oncogene Proteins c-aktmetabolismUp-RegulationAKT/ERK signaling pathwayGBX2invasion and migrationlung adenocarcinomaproliferation201991020191172019112020191124602021515602019112460ppublish3175872610.1002/jgm.3147REFERENCESSiegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69:7-34.The Cancer Genome Atlas Research Network. Comprehensive molecular profiling of lung adenocarcinoma. 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