摘要
Objective: Currently, no satisfactory targets for colorectal cancer or markers for immunotherapy and diagnosis and prognosis are available. Immunoglobulin G(Ig G) is widely expressed in many cancers, and it promotes cancer progression. This study explored the role of cancer-derived Ig G(CIg G) in colorectal cancer.Methods: First, using a monoclonal antibody to CIg G, we examined the expression levels of CIg G in colorectal cancer cell lines by western blot and immunofluorescence analyses and in tissue specimens by immunohistochemistry. Second, the variable region gene was amplified by nested polymerase chain reaction(PCR), and PCR products were sequenced and analyzed. Third, we investigated the effect of CIg G on colorectal cancer cells by cell proliferation, wound healing, migration and invasion assays, and colony formation assay. Fourth, we performed in vivo tumorigenicity experiments to explore the effect of CIg G on tumorigenicity. Finally, we used RNA-seq analysis and co-immunoprecipitation experiments to further clarify possible mechanisms of CIg G.Results: We found that CIg G is widely expressed in colorectal cancer cells, and the overexpression of CIg G indicates significantly poor colorectal cancer prognosis. Furthermore, CIg G knockdown significantly inhibits the proliferation, migration and invasion ability of cells, and tumor growth in vivo. RNA-seq analysis indicated that CIg G knockdown results primarily in changes in expression of apical junction and epithelial-mesenchymal transition-related genes. CIg G may be involved in colorectal cancer invasion and metastasis through interacting with E-cadherin.Conclusions: CIg G is a potential human oncogene in colorectal cancer and that it has potential for application as a novel target in targeted therapy and a marker for prognostic evaluation.
Objective: Currently, no satisfactory targets for colorectal cancer or markers for immunotherapy and diagnosis and prognosis are available. Immunoglobulin G(Ig G) is widely expressed in many cancers, and it promotes cancer progression. This study explored the role of cancer-derived Ig G(CIg G) in colorectal cancer.Methods: First, using a monoclonal antibody to CIg G, we examined the expression levels of CIg G in colorectal cancer cell lines by western blot and immunofluorescence analyses and in tissue specimens by immunohistochemistry. Second, the variable region gene was amplified by nested polymerase chain reaction(PCR), and PCR products were sequenced and analyzed. Third, we investigated the effect of CIg G on colorectal cancer cells by cell proliferation, wound healing, migration and invasion assays, and colony formation assay. Fourth, we performed in vivo tumorigenicity experiments to explore the effect of CIg G on tumorigenicity. Finally, we used RNA-seq analysis and co-immunoprecipitation experiments to further clarify possible mechanisms of CIg G.Results: We found that CIg G is widely expressed in colorectal cancer cells, and the overexpression of CIg G indicates significantly poor colorectal cancer prognosis. Furthermore, CIg G knockdown significantly inhibits the proliferation, migration and invasion ability of cells, and tumor growth in vivo. RNA-seq analysis indicated that CIg G knockdown results primarily in changes in expression of apical junction and epithelial-mesenchymal transition-related genes. CIg G may be involved in colorectal cancer invasion and metastasis through interacting with E-cadherin.Conclusions: CIg G is a potential human oncogene in colorectal cancer and that it has potential for application as a novel target in targeted therapy and a marker for prognostic evaluation.
基金
supported by grants from the National Natural Science Foundation of China (No. 8157101395)
Beijing Natural Science Foundation (No. 7182171)
