Cao WenJing, Tan XueYing, Li Xuze, Wang YuLin, Zhai YuQing, Zhang ZongLiang, Yuan JiangShui, Song WeiQing
Department of Medicine, Qingdao University, Qingdao, China.
Department of Clinical Laboratory, Qingdao Municipal Hospital, Qingdao, China.
Med Oncol. 2025 Apr 9;42(5):156. doi: 10.1007/s12032-025-02704-6.
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.
MIS18结合蛋白1（MIS18BP1）是MIS18复合体的一个亚基，特异性地聚集在末期-G1期着丝粒处，并调节癌细胞的凋亡、增殖和迁移。此前，关于MIS18BP1如何调节膀胱癌（BCa）细胞发育的机制尚不清楚。我们通过癌症基因组图谱（TCGA）、基因表达综合数据库（GEO）和通用蛋白质数据库分析了MIS18BP1在BCa中的差异表达。使用qRT-PCR检测MIS18BP1 mRNA的表达。通过蛋白质免疫印迹法和免疫组织化学（IHC）染色检测MIS18BP1蛋白的表达。用LV-MIS18BP1-RNAi载体转染T24细胞以降低MIS18BP1的表达。我们进行了一系列实验来检测T24细胞的存活、增殖和迁移情况。通过流式细胞术分析细胞凋亡。通过蛋白质免疫印迹法检测P53、BAX和裂解的半胱天冬酶-3的表达。在用P53抑制剂处理前后，分析细胞的P53凋亡相关蛋白、增殖和迁移情况。与对照组相比，BCa组织中MIS18BP1的表达更高。其表达与临床分期、浸润深度和淋巴结转移有关。我们发现与MIS18BP1密切相关的基因在生物学过程中主要与细胞周期、染色体分离和DNA修复相关。转染后，我们发现T24细胞的增殖能力显著降低。Transwell迁移实验和划痕实验表明细胞迁移减少。同时，MIS18BP1的下调导致细胞凋亡增加。此外，在MIS18BP1下调的T24细胞中，P53、BAX和裂解的半胱天冬酶-3增加，而BCL2蛋白减少。用pifithrin-α处理后，细胞增殖抑制表型得以恢复。MIS18BP1的过表达可能与BCa患者的不良预后相关。MIS18BP1可能与BC细胞的凋亡和增殖有关。这一过程可能由P53信号通路介导。
