Di-Jian Shen1, You-Hua Jiang1, Jian-Qiang Li1, Li-Wei Xu1, Kai-Yi Tao2. 1. Department of Thoracic Surgery, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, No. 1 Banshan East Road, Gongshu District, Hangzhou, 310022, China. 2. Department of Thoracic Surgery, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, No. 1 Banshan East Road, Gongshu District, Hangzhou, 310022, China. Electronic address: taoky@zjcc.org.cn.
Abstract
BACKGROUND: Non-small-cell lung cancer (NSCLC) remains a highly prevalent and deadly form of cancer, with efforts to better understand the molecular basis of the progression of this disease being essential to its effective treatment. Several recent studies have highlighted the ability of RNA-binding proteins (RBPs) to regulate a wide range of cellular processes in both healthy and pathogenic contexts. Among these RBPs, RNA binding motif protein 47 (RBM47) has recently been identified as a tumor suppressor in both breast and colon cancers, whereas its role in NSCLC is poorly understood. METHODS: RBM47 expression in NSCLC samples was evaluated by RT-PCR, western blotting and immunohistochemistry analysis. Molecular and cellular techniques including lentiviral vector-mediated knockdown were used to elucidate the functions and mechanisms of RBM47. RESULTS: This study sought to analyze the expression and role of RBM47 in NSCLC. In the present study, we observed reduced levels of RBM47 expression in NSCLC, with these reductions corresponding to a poorer prognosis and more advanced disease including a higher TNM stage (p = 0.022), a higher likelihood of tumor thrombus (p = 0.001), and pleural invasion (p = 0.033). Through functional analyses in vitro and in vivo, we further demonstrated that these RBP was able to disrupt the proliferation, migration, and invasion of NSCLC cells. At a molecular level, we determined that RBM47 was able to bind the AXIN1 mRNA, stabilizing it and thereby enhancing the consequent suppression of Wnt/β-catentin signaling. CONCLUSION: Together our findings reveal that RBM47 targets AXIN1 in order to disrupt Wnt/β-catenin signaling in NSCLC and thereby disrupting tumor progression. These results thus offer new insights into the molecular biology of NSCLC, and suggest that RBM47 may also have value as a prognostic biomarker and/or therapeutic target in NSCLC patients.
BACKGROUND:Non-small-cell lung cancer (NSCLC) remains a highly prevalent and deadly form of cancer, with efforts to better understand the molecular basis of the progression of this disease being essential to its effective treatment. Several recent studies have highlighted the ability of RNA-binding proteins (RBPs) to regulate a wide range of cellular processes in both healthy and pathogenic contexts. Among these RBPs, RNA binding motif protein 47 (RBM47) has recently been identified as a tumor suppressor in both breast and colon cancers, whereas its role in NSCLC is poorly understood. METHODS:RBM47 expression in NSCLC samples was evaluated by RT-PCR, western blotting and immunohistochemistry analysis. Molecular and cellular techniques including lentiviral vector-mediated knockdown were used to elucidate the functions and mechanisms of RBM47. RESULTS: This study sought to analyze the expression and role of RBM47 in NSCLC. In the present study, we observed reduced levels of RBM47 expression in NSCLC, with these reductions corresponding to a poorer prognosis and more advanced disease including a higher TNM stage (p = 0.022), a higher likelihood of tumor thrombus (p = 0.001), and pleural invasion (p = 0.033). Through functional analyses in vitro and in vivo, we further demonstrated that these RBP was able to disrupt the proliferation, migration, and invasion of NSCLC cells. At a molecular level, we determined that RBM47 was able to bind the AXIN1 mRNA, stabilizing it and thereby enhancing the consequent suppression of Wnt/β-catentin signaling. CONCLUSION: Together our findings reveal that RBM47 targets AXIN1 in order to disrupt Wnt/β-catenin signaling in NSCLC and thereby disrupting tumor progression. These results thus offer new insights into the molecular biology of NSCLC, and suggest that RBM47 may also have value as a prognostic biomarker and/or therapeutic target in NSCLCpatients.