A novel FoxM1-PSMB4 axis contributes to proliferation and progression of cervical cancer

The abnormally high activity of the proteasome system is closely related to the occurrence and development of various tumors. PSMB4 is a non-catalytic subunit for the proteasome assembly. Although the reports from genetic screening have demonstrated it's a driver gene for cell growth in several types of solid tumor, its expression pattern and regulatory mechanisms in malignant diseases are still elusive. Here, we found that PSMB4 is overexpressed in cervical cancer tissues. And knockdown of PSMB4 significantly inhibited cervical cancer cell proliferation. The mechanistic study revealed that FoxM1, a master regulator of cell division, binds directly to the promoter region of PSMB4 and regulates the PSMB4 expression in the mRNA level. In addition, the data analysis from TCGA showed a positive correlation between FxoM1 and PSMB4 in cervical cancer. Furthermore, the loss of functional and rescue experiments confirmed that PSMB4 is required for FoxM1-driven cervical cancer cell proliferation. Collectively, our study explains the phenomenon of dysregulated expression of PSMB4 in cervical cancer tissues and verifies its driver effect on cancer cell proliferation. More importantly, it highlights a FoxM1-PSMB4 axis could be a potential target for the treatment of cervical cancer.