ABSTRACT
Although radiation therapy is the primary treatment for nasopharyngeal carcinoma, radioresistance remains a major obstacle to successful treatment in many cases, and the exact underlying molecular mechanisms are still ill-defined. EMP2, epithelial membrane protein-2, was a recently identified potential oncogene involved in multiple biological processes including cell migration and cell proliferation. This study was to explore the potential relationship between EMP2 expression, nasopharyngeal carcinoma genesis, and radioresistance. EMP2 expression status in 98 nasopharyngeal carcinoma clinical samples was examined by immunohistochemical staining. As a result, most of the nasopharyngeal carcinoma tumor samples were weakly or negatively stained, while paired adjacent normal tissues were moderately or strongly stained. Moreover, patients with higher expression of EMP2 had significant longer survival times. EMP2 re-expression suppresses cell growth, induces S-phase cell cycle arrest, and promotes radiosensitivity and apoptosis in nasopharyngeal carcinoma cells. These results support that loss of EMP2 is common, and its re-expression may serve as an approach to enhance radiation sensitivity in nasopharyngeal carcinoma.
Subject(s)
Cell Proliferation/genetics , Membrane Glycoproteins/biosynthesis , Nasopharyngeal Neoplasms/radiotherapy , Radiation Tolerance/genetics , Adult , Aged , Apoptosis/genetics , Carcinoma , Cell Cycle Checkpoints/genetics , Cell Line, Tumor/drug effects , Cell Movement/genetics , Cell Proliferation/radiation effects , Gene Expression Regulation, Neoplastic , Humans , Membrane Glycoproteins/genetics , Middle Aged , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms/genetics , Nasopharyngeal Neoplasms/pathologyABSTRACT
Biot2 is a tumor-associated antigen, and it is a novel gene (GenBank EF100607) that was first identified with the SEREX technique and named by our laboratory. It is highly expressed in cancer cells and testis, with low or no expression in normal tissues. In our previous study, RNA interference of human Biot2 can inhibit tumor cell growth, and it is associated with poor prognosis of patients in clinical study; however, the mechanism of Biot2 that effects tumor growth is not yet clear. Here, in this study, we explore further the mechanism of Biot2 by silencing Biot2 in CT26 cells. It provides some theoretical basis for Biot2 as a new target for gene therapy. In CT26 cells, the expression of Biot2 was downregulated by Biot2-shRNA. It also promoted G1 phase arrest, the expression of p16 and p21, and cell apoptosis. In the mouse model, the tumor volume and the expression of PCNA of the Biot2-shRNA group significantly decreased. These results suggest that silencing Biot2 in CT26 cells by RNA interference can inhibit cell growth in vitro and in vivo. It also induces cell cycle arrest in the G1 phase and apoptosis throughout regulation of p16 and p21. Taken together, our data demonstrate that Biot2 can be a potential target of gene therapy.
Subject(s)
Antigens, Neoplasm/genetics , Apoptosis/genetics , G1 Phase Cell Cycle Checkpoints/genetics , Gene Expression Regulation, Neoplastic , RNA Interference , Animals , Cell Line, Tumor , Cell Proliferation , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Genes, p53 , Male , Mice , RNA, Small Interfering , Tumor BurdenABSTRACT
Here, we investigated the molecular mechanism underlying the changes in the distribution of nucleolin. Our study identified PI3K/Akt signaling as an essential pathway regulating the distribution of nucleolin. Furthermore, nucleolin can interact with phospho-PI3K-p55, and changes in the distribution of nucleolin were related to its phosphorylation. Subsequently, we analyzed the correlation of VEGF and nucleolin, and found that distribution of nucleolin related to metastatic potential. Finally, blocking cell surface nucleolin influences the process of epithelial-mesenchymal transitions. This indicates that nucleolin may be a novel cancer therapy target and a predictive marker for tumor migration in colorectal carcinoma.
