Circular RNA VANGL1 knockdown suppressed viability, promoted apoptosis, and increased doxorubicin sensitivity through targeting miR-145-5p to regulate SOX4 in bladder cancer cells

Abstract

Abstract Background Bladder cancer is a common malignancy in the world. It is reported that circular RNA VANGL1 (circ_VANGL1) was involved in bladder cancer progression. However, the functional role and molecular mechanism of circ_VANGL1 in bladder cancer were still unclear. Methods The levels of circ_VANGL1, microRNA-145-5p (miR-145-5p), and Sex-determining region Y-related high-mobility group box 4 (SOX4) in bladder cancer tissues and cells were determined by quantitative real-time polymerase chain (RT-qPCR). The relative protein expression was detected by western blot. Cell counting kit-8 (CCK8) and flow cytometry analysis were used to measure cell viability, IC50 value, and apoptosis rate. The interaction between miR-145-5p and circ_VANGL1 or SOX4 was predicted by online software starBase v2.0 or Targetscan and verified by the dual-luciferase reporter assay. Besides, xenograft mice model was used to detect the effects of circ_VANGL1 in vivo. Results The level of circ_VANGL1 and SOX4 was increased, while miR-145-5p was decreased in bladder cancer tissues and cells. Knockdown of circ_VANGL1 suppressed viability, while promoted apoptosis and increased doxorubicin sensitivity in bladder cancer cells. Moreover, circ_VANGL1 acted as a sponge for miR-145-5p. In addition, miR-145-5p partially reversed the effects of miR-145-5p knockdown in T24 and J82 cells. SOX4 was a target of miR-145-5p and negatively regulated by miR-145-5p. Furthermore, miR-145-5p regulated SOX4 to affect cell progression in bladder cancer cells, including viability, apoptosis, and doxorubicin sensitivity. Besides, circ_VANGL1 suppressed tumor growth and enhanced the doxorubicin sensitivity in bladder cancer in vivo. Conclusion circ_VANGL1 mediated cell viability, apoptosis, and doxorubicin sensitivity by regulating miR-145-5p/SOX4 axis in bladder cancer, providing a potential therapeutic target for bladder cancer therapy.