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Oncoprotein HBxiP promotes tumorigenesis through MAPK/ERK pathway activation in non-small cell lung cancer

cancer Biology & Medicine 2021年第1期18卷 105-119页

作者： Jun Zhang Bei Sun xianhui Ruan xiukun Hou Jingtai Zhi xiangrui Meng xiangqian Zheng Ming Gao Department of Breast cancer Key Laboratory of Breast Cancer Prevention and TherapyTianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China Department of Outpatient Office Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China Department of Thyroid and Neck Tumor Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China Department of Lymphoma Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China

Objective:The oncoprotein,hepatitis B X-interacting protein(HBxiP),has been reported to play an important role in human ***,its functions in non-small cell lung cancer(NSCLC)are poorly *** goal of the present study was to identify the role of HBxiP in the regulation of NSCLC ***:The level of HBxiP expression in NSCLC tissue was assessed by immunohistochemical and Western blot analyses,and its relationships with clinicopathological features and outcomes were statistically *** effects of HBxiP on NSCLC cell progression were assessed through cell viability,colony formation,and flow cytometry analyses in *** mechanism by which HBxiP regulated the MAPK pathway was studied by Western blot,immunofluorescence,and immunoprecipitation *** addition,in vivo experiments were performed to evaluate the progression of NSCLC and ERK signaling pathway activation after HBxiP ***:HBxiP was overexpressed in human NSCLC and was correlated with the invasiveness of *** high expression of HBxiP in NSCLC was significantly correlated with gender(P=0.033),N stage(P=0.002),and tumor-node-metastasis stage(P=0.008).In vitro experiments using an NSCLC cell line revealed that HBxiP knockdown resulted in the suppression of cell proliferation and colony formation,which was consistent with the enhanced cell cycle arrest in G1 *** results of a mechanistic investigation suggested that binding of HBxiP to MEK1 protein promoted MAPK/ERK signaling pathway activation in NSCLC by preventing the proteasome-mediated degradation of *** addition,the results obtained using in vivo subcutaneous tumor xenografts confirmed that HBxiP deficiency decreased MEK1 protein levels and NSCLC tumor ***:Taken together,our results showed that the HBxiP-MEK interaction promoted oncogenesis via the MAPK/ERK pathway,which may serve as a novel therapeutic target for cancers in which MAPK/ERK signaling is a dominant featur

关键词： HBxiP non-small cell lung cancer MEK1 tumor progression

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