MIS18BP1 promotes bladder cancer cell proliferation and growth via inactivating P53 signaling pathway.

MIS18 bonding protein 1 (MIS18BP1) is a subunit of MIS18 complex, accumulated specifically at telophase-G1 centromere and regulated apoptosis, proliferation and migration in cancer cells. The mechanisms about how MIS18BP1 regulate Bladder Cancer (BCa) cell development have not been previously unknown. We analyzed MIS18BP1 differential expression in BCa by The Cancer Genome Atlas (TCGA), Gene-Expression Omnibus (GEO) and Universal Protein database. The expression of MIS18BP1 mRNA was tested using qRT-PCR. The expression of MIS18BP1 protein was examined by western blot and immunohistochemistry (IHC) staining. T24 cells were transfected with an LV -MIS18BP1 -RNAi vector to decrease the MIS18BP1 expression. We used a series of experiments to detect the survival, proliferation and migration of T24. The apoptosis was analyzed by Flow cytometry assays. The expression of P53, BAX and Cleaved Casepase-3 was detected by western blot. P53 apoptosis-related proteins, proliferation and migration of cells were analyzed before and after treatment with P53 inhibitors. The expression of MIS18BP1 was higher in BCa tissues compared with control group. Its expression was in relation to clinical stage, depth of invasion and lymph node metastasis. We found that genes closely related to MIS18BP1 are mainly associated with cell cycle, chromosome separation and DNA repair in biological processes. After transfection, we found the proliferative capacity of T24 was significantly reduced. Transwell migration and scratch experiment demonstrated decreased migration. Meanwhile, downregulation of MIS18BP1 resulted in an increase in cell apoptosis. In addition, P53, BAX and Cleaved Casepase-3 were increased, whereas BCL2 protein was decreased in the MIS18BP1-downregulated T24. After treatment with Pifithrin-α, the phenotype of cell proliferation inhibition was restored. MIS18BP1 overexpression may be regulated to poor prognosis in BCa patients. MIS18BP1 may associated with cell apoptosis and proliferation in BC cells. This process may be mediated by P53 signal pathway.