FBXO45 Knockdown Restrains the Progression of Bladder Cancer via the ERK/Cyclin D1/CDK4 Pathway.

Abstract

F-box protein 45 (FBXO45) has been implicated in the progression of several diseases. Whether FBXO45 is involved in the development of bladder cancer remains unclear. Thus, this study focused on the effect of FBXO45 on the malignant progression of bladder cancer cells. FBXO45 small-interference fragment was transfected into RT4 and 5637 cells by liposome-mediated transfection, and the knockdown efficiency of FBXO45 was verified by Western blot assay. The growth rate between FBXO45 knockdown cell lines and control cell lines was compared by counting kit 8 and plate cloning experiments. The motility of bladder cancer cells was observed via the Transwell test and Wound healing test. The effects of FBXO45 silencing on apoptosis and cell division were confirmed by flow cytometry. Western blot assay was performed to determine the function of FBXO45 knockdown on key proteins of cell apoptosis and the ERK/Cyclin D1/CDK4 pathway. After FBXO45 knockdown, the proliferation of bladder cancer cells was blocked (p < 0.01), and the migration and invasion abilities were reduced (p < 0.01). FBXO45 knockdown reduced the number of S-phase cells (RT4, p < 0.01; 5637, p < 0.05) and enhanced the apoptotic rate (p < 0.01). FBXO45 knockdown decreased the levels of p-ERK1/2, CDK4 and Cyclin D1 (p < 0.01). This study revealed that FBXO45 plays a carcinogenic role in bladder cancer via the ERK/Cyclin D1/CDK4 pathway, which provides a reference for the clinical treatment of patients with bladder cancer.