Rui Yang1, Ping Li1, Guojun Zhang1, Chunya Lu1, Huaqi Wang1, Guoqiang Zhao2. 1. Department of Respiratory Medicine, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, China. 2. Department of Microbiology and Immunology, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.
Abstract
BACKGROUND: The therapy and prognosis of lung cancer are difficult because of multiple genetic and epigenetic alterations. Long non-coding RNAs (lncRNAs) have been verified as new mediators of cancer development and progression by virtue of their various functions. Here, we focused on the lncRNA XLOC_008466 based on previous microarray data. However, whether aberrant expression of XLOC_008466 in human non-small cell lung cancer (NSCLC) is correlated with malignancy, metastasis or prognosis has not been elucidated. METHODS: We performed real-time PCR, CCK-8, flow cytometry, trans-well, western blotting, luciferase reporter assays, RNA immunoprecipitation (RIP) assay and surface plasmon resonance (SPR) assay to detect the function of XLOC_008466 in NSCLC. RESULTS: Up-regulation of XLOC_008466 in NSCLC patients was related to lymph node metastasis and the TNM stage. In vitro, down-regulation of XLOC_008466 inhibited cell proliferation and invasion of A549 and H460 cells in vitro, but promoted cell apoptosis. Experiments on mechanisms revealed that XLOC_008466 functioned as a ceRNA, directly binding to miR-874, and could affect cell proliferation, apoptosis and invasion through regulation of miR-874 expression as well as by increasing matrix metalloproteinase 2 (MMP2) and X-linked inhibitor of apoptosis (XIAP) expression. CONCLUSIONS: XLOC_008466 functions as an oncogene in NSCLC by regulating the miR-874-MMP2/XIAP axis, which indicates that XLOC_008466 may be a useful marker and potential therapeutic target in NSCLC.
BACKGROUND: The therapy and prognosis of lung cancer are difficult because of multiple genetic and epigenetic alterations. Long non-coding RNAs (lncRNAs) have been verified as new mediators of cancer development and progression by virtue of their various functions. Here, we focused on the lncRNA XLOC_008466 based on previous microarray data. However, whether aberrant expression of XLOC_008466 in humannon-small cell lung cancer (NSCLC) is correlated with malignancy, metastasis or prognosis has not been elucidated. METHODS: We performed real-time PCR, CCK-8, flow cytometry, trans-well, western blotting, luciferase reporter assays, RNA immunoprecipitation (RIP) assay and surface plasmon resonance (SPR) assay to detect the function of XLOC_008466 in NSCLC. RESULTS: Up-regulation of XLOC_008466 in NSCLCpatients was related to lymph node metastasis and the TNM stage. In vitro, down-regulation of XLOC_008466 inhibited cell proliferation and invasion of A549 and H460 cells in vitro, but promoted cell apoptosis. Experiments on mechanisms revealed that XLOC_008466 functioned as a ceRNA, directly binding to miR-874, and could affect cell proliferation, apoptosis and invasion through regulation of miR-874 expression as well as by increasing matrix metalloproteinase 2 (MMP2) and X-linked inhibitor of apoptosis (XIAP) expression. CONCLUSIONS: XLOC_008466 functions as an oncogene in NSCLC by regulating the miR-874-MMP2/XIAP axis, which indicates that XLOC_008466 may be a useful marker and potential therapeutic target in NSCLC.