The Research On The Roles And Mechanismsof BEX2 In Proliferation And Metastasis Of Colorectal Cancer

PurposeBex2 (Brain expressed X-linked protein 2) belongs to IDPs (Instrinsically Disordered Proteins), containing about 128 amino acids, which plays an important role in transcriptional regulation, cell cycle, differentiation, proliferation and tumor signaling pathway. In recent years, studies had reported that Bex2 was asscociated with tumorigenesis, which played different functions in different types of tumors. The functions and mechanisms of Bex2 in colorectal cancer have not yet been reported. The Research on the Roles and Mechanisms of BEX2 in Colorectal Cancer can explore the molecular events of CRC biology, which will facilitate the discovery of novel therapeutic target.Methods and Contents:We explored correlation of the BEX2 expression and the colorectal cancer characteristics by utilizing the GSE14333 database, and the relationship between BEX2 expression and clinical characterics was verified by detecting the BEX2 expression in 34 cases of fresh colorectal cancer tissues. Moreover, cell proliferation assay, clone formation assay, cell migration, cell invasion, xenografted model and tumor liver metastasis model were employed in exploring the roles of BEX2 in colorectal cancer. Bioinformatics analysis, western blot and gene chip were combined to identify the possible downstream key regulatory mechanisms caused by the BEX2. This study could enrich the content of colorectal cancer research. It could not only partly illustrate the molecular mechanisms of the development of colorectal cancer, but also provide possible targets for gene therapy.Results:This was the first study to explore the relationship between the BEX2 expression and the stage of colorectal cancer. we found that BEX2 expression in colorectal cancer was positively correlated with the TNM stage. The in vitro and in vivo experiments proved that silencing BEX2 can inhibit colon cancer cell proliferation, colony formation ability and tumorigenicity. The phosphorylation of JNK and c-Jun expression was silenced after the BEX2 knockdown in the colorectal cancer, while Erk and p-38 were not changed. Meanwhile, selective JNK inhibitor SP600125 was added in control cells significantly inhibiting cell proliferation. Western blot was used to confirm that the phosphorylation of JNK in non-silent BEX2 cells was occurred. Meanwhile, we found that BEX2 knockdown can inhibit colon cancer cell migration, and the colorectal cancer orthotopic model and semi-spleen liver metastasis model experiments showed that BEX2 knockout could significantly prolong survival in BEX2 knockout liver metastasis model group. Moreover, the process was not dependent with EMT and the gene chip suggested that a series of MMP gene may be associated with the process.Conclusions and InnovationsBex2 was asscociated with tumorigenesis, which played different functions in different types of tumors. While, the functions and mechanisms of Bex2 in colorectal cancer have not yet been reported. Deep understanding of the role of Bex2 in colorectal cancer not only can further explore the development of epigenetic molecular mechanisms of colorectal cancer, but also provide new targets and ideas for colorectal cancer gene therapy.1.We extracted the data from the GEO database by the systemic bioinformatics technology explore the relationship between BEX2 expression and the characteristics of colorectal cancer, then verified by a mass of colorectal cancer tissues. We firstly proved that BEX2 expression in colorectal cancer was positively correlated with the TNM stage.2. We constructed the BEX2 knockdown cell. For the first time, we found that the cell proliferation, clone ability and animal tumorigenicity of colorectal cancer cell were significantly reduced through MAPK/JNK signaling pathway after BEX2 knockdown.3. We provided some grounds for the study of the role of liver metastases in colorectal cancer, we had successfully established a colorectal cancer orthotopic model and semi-spleen liver metastasis model and found that BEX2 knockdown could inhibit liver cancer metastasis. The process was not dependent on the EMT process, and the gene chip data suggested that may be associated with the MMP family...