MYBL2 promotes proliferation and metastasis of bladder cancer through transactivation of CDCA3

The transcription factor MYB proto-oncogene like 2 (MYBL2) is critical in regulating gene expression and tumorigenesis. However, the biological function of MYBL2 in bladder cancer (BLCA) remains to be elucidated. Here, we first revealed that MYBL2 was elevated in BLCA tissues and significantly correlated with clinicopathological parameters and cancer-specific survival in BLCA patients. Phenotypic assays showed that MYBL2 deficiency suppressed the proliferation and migration of BLCA cells in vitro and in vivo, whereas MYBL2 overexpression contributed to the opposite phenotype. Mechanistically, MYBL2 could bind to the promoter of its downstream target gene cell division cycle-associated protein 3 (CDCA3) and transactivate it, which in turn promoted the malignant phenotype of BLCA cells. Further investigations revealed that MYBL2 interacted with forkhead box M1 (FOXM1) to co-regulate the transcription of CDCA3. In addition, MYBL2/FOXM1 and CDCA3 might activate Wnt/beta-catenin signaling, thereby promoting the malignant phenotype of BLCA cells. In conclusion, the current study identifies MYBL2 as an oncogene in BLCA. MYBL2 can accelerate the proliferation and metastasis of BLCA through the transactivation of CDCA3.

Automated summary

The study reveals that MYBL2 is elevated in bladder cancer and significantly correlated with clinicopathological parameters and patient survival. MYBL2 deficiency suppresses the proliferation and migration of bladder cancer cells, while MYBL2 overexpression promotes these phenotypes. Mechanistically, MYBL2 can bind to the promoter of CDCA3 and activate its transcription, thereby promoting the malignant phenotype of bladder cancer cells. Furthermore, MYBL2 interacts with FOXM1 to co-regulate CDCA3 transcription and activate Wnt/beta-catenin signaling, contributing to the malignant phenotype of bladder cancer.