Yi Zheng1, Hui You1, Jingzhu Duan1, Biyu Chen1, Chenlin Wu1, Peipei Chen1, Meifang Wang2. 1. Department of Respiratory and Critical Care Medicine, Taihe Hospital, Hubei University of Medicine, No. 32, Renmin South Road, Maojian District, Shiyan, 442000, Hubei, China. 2. Department of Respiratory and Critical Care Medicine, Taihe Hospital, Hubei University of Medicine, No. 32, Renmin South Road, Maojian District, Shiyan, 442000, Hubei, China. wangmeifangwmf@163.com.
Abstract
BACKGROUND: As an important member of centromere family, centromere associated protein N (CENPN) was abnormally expressed in varied malignant tumors. OBJECTIVE: This paper aimed to analyze the expression and related mechanism of CENPN in lung adenocarcinoma (LUAD). METHODS: The expression of CENPN in LUAD was analyzed by Gene Expression Profiling Interactive Analysis (GEPIA) database. The mRNA expression, protein expression, cell viability, cell invasion, cell apoptosis, cell stem like characteristics were detected by RT-PCR, western blot, CCK8 assay, transwell assay, flow cytometry and spheroidization assay, respectively. Finally, the pathological changes of xenograft were estimated by H&E staining, and the expression of proteins was detected by immunohistochemistry. RESULTS: GEPIA analysis showed that the CENPN expression in LUAD was significantly higher than that in normal lung tissue, which was negatively correlated with the prognosis. These results were consistent with our clinical data. Besides, CENPN was highly expressed in LUAD cell lines. In addition, the upregulation of CENPN amplified the cell viability, stemness and invasive ability in PC9 cells. However, the knockdown of CENPN inhibited the cell activity, stemness, invasive ability with increased cell apoptosis in A549. Furthermore, CENPN could positively regulate the phosphorylation of PI3K and AKT. The PI3K inhibitor, 740Y-P, could reverse the effect of CENPN silencing on the expression of Ki-67, cleaved caspase 3, OCT4, and snail 1. Finally, the downregulation of CENPN restrained the growth of xenograft and inactivated the PI3K/AKT pathway. CONCLUSION: CENPN was abnormally overexpressed in LUAD, and promoted tumor progression of LUAD by affecting PI3K/AKT pathway.
BACKGROUND: As an important member of centromere family, centromere associated protein N (CENPN) was abnormally expressed in varied malignant tumors. OBJECTIVE: This paper aimed to analyze the expression and related mechanism of CENPN in lung adenocarcinoma (LUAD). METHODS: The expression of CENPN in LUAD was analyzed by Gene Expression Profiling Interactive Analysis (GEPIA) database. The mRNA expression, protein expression, cell viability, cell invasion, cell apoptosis, cell stem like characteristics were detected by RT-PCR, western blot, CCK8 assay, transwell assay, flow cytometry and spheroidization assay, respectively. Finally, the pathological changes of xenograft were estimated by H&E staining, and the expression of proteins was detected by immunohistochemistry. RESULTS: GEPIA analysis showed that the CENPN expression in LUAD was significantly higher than that in normal lung tissue, which was negatively correlated with the prognosis. These results were consistent with our clinical data. Besides, CENPN was highly expressed in LUAD cell lines. In addition, the upregulation of CENPN amplified the cell viability, stemness and invasive ability in PC9 cells. However, the knockdown of CENPN inhibited the cell activity, stemness, invasive ability with increased cell apoptosis in A549. Furthermore, CENPN could positively regulate the phosphorylation of PI3K and AKT. The PI3K inhibitor, 740Y-P, could reverse the effect of CENPN silencing on the expression of Ki-67, cleaved caspase 3, OCT4, and snail 1. Finally, the downregulation of CENPN restrained the growth of xenograft and inactivated the PI3K/AKT pathway. CONCLUSION: CENPN was abnormally overexpressed in LUAD, and promoted tumor progression of LUAD by affecting PI3K/AKT pathway.
Authors: Juan Angel Fresno Vara; Enrique Casado; Javier de Castro; Paloma Cejas; Cristóbal Belda-Iniesta; Manuel González-Barón Journal: Cancer Treat Rev Date: 2004-04 Impact factor: 12.111
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