The Discussion Of Biological Function Of CTA FBXO39 In Tumor Cells

CTA(Cancer-testis antigen), a popular target for immunotherapy, is one of tumor-associated antigens with specific expression profile. FBXO39 protein, as a CTA, has F-box domain and it belongs to F-box protein family.However, its functions in cell are still unknown because of lack of related research. It has been well-known that many F-box proteins play important roles in the regulation of biological activities of tumor, such as cell cycle, repairing DNA damage, metabolism regulationand so on. As one of F-box family proteins, we speculated that FBXO39 might have similar functions. In order to make a preliminary exploration on the function of FBXO39 in cancer, the following three aspects were carried out in this thesis:1. The level of FBXO39 expression in human normal tissues, tumor tissues and cancer adjacent tissues of multiple organs were detected by tissue microarray-immunohistochemistry. The results showed that FBXO39 has a higher expression level in tumor tissues and cancer adjacent tissues, compared with in normal tissues. Also, the high tumor clinical grades were correlated with the high expression of FBXO39. These results suggested FBXO39 might be an oncogene.2. The biological effects of FBXO39 were analyzed in cancer cells. A recombinant eukaryotic vector of FBXO39wa.s constructed and then transfected in MCF7 cells. We found that the overexpression of FBXO39 had little influence on cell proliferation, cell cycle, cell apoptosis through MTT, FACS methods. In the meantime,bioinformatic analysis showed that there are multiple DNA damage related transcription factor binding sites in the core promoter region of FBXO39, which suggested FBXO39 might involve in DNA damage response. Using qPCR and western blot, we confirmed that FBXO39 could be upregulated under DNA damage induced by UV-C. This indicated that it function in the DDR (DNA damage response) of tumor cells.3. High throughput PCR array were performed to study the connection between FBXO39 and metabolism-related genes in MCF7 cells. And the selected genes were further verified in Ntera2 cells. The result showed ACDH9A1, MCTI, DLAT, HMGCS, FASN and GLUL could be upregulated by overexpression ofFBXO39.In conclusion, FBXO39 has a higher expression level in tumor tissues and cancer adjacent tissues than that in normal tissues, which suggested it might be an oncogene. FBXO39 might function in the DDR and cancer metabolism. The results in our study will be helpful for the further study of functions of FBXO39.