Abstract
BackgroundBladder 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.MethodsThe 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.ResultsThe 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.Conclusioncirc_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.
Highlights
It was reported that there were an estimated 74,690 new cases and 15,580 deaths due to bladder cancer in 2014 in USA [1]
The results suggested that T24 and J82 cells transfected with si-circ#1 or si-circ#2 exhibited lower cell viability (Figure 2b) and increased cell apoptosis rate in bladder cancer cells (Figure 2c)
The results revealed that circ_VANGL1 knockdown decreased cell survival rate and IC50 value of doxorubicin in the T24 and J82 cells, which was shown by a statistical difference between the si-NC group and si-circ#1 or si-circ#2 group (Figure 2d and e)
Summary
It was reported that there were an estimated 74,690 new cases and 15,580 deaths due to bladder cancer in 2014 in USA [1]. A previous research indicated that circRIP2 exerted promotion effects on epithelial-mesenchymal transition in bladder cancer cells [3]. CircRNA ITCH suppressed bladder cancer development through regulating the. Effect of circular RNA VANGL1/bladder cancer cells 1011 expression of p21 and PTEN by targeting miR-224/miR-17 [4]. Present evidence demonstrated that miRNAs play vital roles in various biological processes, including cell proliferation, apoptosis, and migration in human cancers [8,9]. Whether miR-145-5p participated in the regulatory mechanism of circ_VANGL1 in bladder cancer is still unclear. The expression of circ_VANGL1 in bladder cancer tissues and cells was detected. We explored the functional role of circ_VANGL1 and its potential regulatory mechanism in the progression of bladder cancer
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