Abstract
Objective
The malignant transformation of normal bladder cells (SV-HUC-1) was induced by arsenite to explore the possible mechanism of circRNA-100284 influencing bladder cancer cell proliferation.
Methods
Normal bladder SV-HUC-1 cells were cultured with 2 μM arsenite to induce malignant transformation. After 0, 3, 6, 12, and 24 h of culture, the expression level of circRNA-100284 in cells was detected by quantitative real-time PCR. Western blotting assays were used to detect the expression levels of EZH2 and cyclin-D1 proteins in cells treated with different media. Cell cycle was analyzed by flow cytometry. In addition, through cell transfection and CCK-8 experiments, the effect and mechanism of circRNA-100284 targeting microRNA-217 on proliferation was determined. The interaction between HSP70 methylation and Aurora-B was determined by Western blotting and immunoprecipitation experiments.
Results
With prolonged contact time with arsenite, the expression level of circRNA-100284 in cells increased continuously (P < 0.05). Western blotting assays showed that the expression levels of EZH2 and cyclin-D1 proteins in arsenite-transformed cells increased. Flow cytometry and CCK-8 showed that circRNA-100284 accelerated cell cycle transition and cell proliferation through miR-217. Finally, after culturing human bladder cancer T24 cells, combined with immunoprecipitation and in vitro kinase experiments, it was found that K561- dimethyl HSP70 activated Aurora-B, thus promoting the proliferation of bladder cancer cells.
Conclusion
CircRNA-100284 activates aurora kinase B by inducing methylation of HSP70 via microRNA-217 to promote the proliferation of bladder cancer cells.
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Data availability
The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.
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ZG J and ZMH contributed to the conception and design of the study; ZMH and HW contributed to the acquisition of data and performed the experiments; ZMH contributed to the analysis of data; ZMH wrote the manuscript; all authors reviewed and approved the final version of the manuscript.
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This research was approved by the Ethics Committee of Peking Union Medical College Hospital. All the procedures were performed in accordance with the 1964 Helsinki Declaration and its later amendments.
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Huang, ZM., Wang, H. & Ji, ZG. CircRNA-100284 activates aurora kinase B by inducing methylation of HSP70 via microRNA-217 to promote proliferation of bladder cancer cells. J Cancer Res Clin Oncol 147, 703–712 (2021). https://doi.org/10.1007/s00432-020-03468-4
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DOI: https://doi.org/10.1007/s00432-020-03468-4