Abstract
Background: Increasing evidence suggests that circular RNAs play a key role in regulating bladder cancer progression. However, this remains to be fully elucidated.Results: In this study, we reanalyzed our previous RNA sequence, and circ5912 was found to downregulate significantly in bladder cancer tissues compared with normal control. Expression of circ5912 inversely correlates with bladder cancer grade, stage, metastasis, and better patient outcomes. In vitro and in vivo, circ5912 has been shown to repress transforming growth factor β signaling, which suppresses proliferation, invasion and migration of bladder cancer induced by mesenchymal-to epithelial transition.Conclusions: Our study firstly demonstrate that circ5912 regulates mesenchymal-to epithelial transition pathway to suppress bladder cancer progression and propose new therapeutic targets and biomarkers for bladder cancer.Materials and Methods: Clinical values of circ5912 in human bladder cancer were examined in a cohort of 58 patients by qPCR. 2 bladder cancer cell lines, T24 and SW780, were used for biological evaluation of circ5912. CCK8, clone formation, wound healing and trans-well assays were performed to determine the in vivo effect of circ5912; a mouse subcutaneous model was designed for in vivo analysis. Western blotting, RNA pulldown assays and florescent in situ hybridization were applied for mechanistic analysis.
Highlights
Bladder cancer is the 7th most frequently diagnosed cancer worldwide [1]
It was observed that circ5912 expression was significantly lower in 45 paired bladder cancer tissues (Figure 1D); in 58 bladder cancer tissues, higher circ5912 levels associates with better clinical pathological conditions, including stage (Figure 1E), tumor grade (Figure 1F) and metastasis (Figure 1G); a longer overall survival time was observed among 43 patients for whom circ5912 was regarded as high (Figure 1H). These results suggest that circ5912 is expressed at lower levels in bladder cancer and that a higher level of circ5912 correlates with better patient outcomes
We found that circ5912 was significantly downregulated in bladder cancer tissues and inversely associated with grade, stage, metastasis, and longer overall survival in bladder cancer patients
Summary
Bladder cancer is the 7th most frequently diagnosed cancer worldwide [1]. Despite recent advances in the early diagnosis of bladder cancer, some undetectable patients progress quickly into having advanced tumors, and the reason behind the progression is not clear [1, 2]. Studies have shown that circular RNAs play an important role in cancer progression [4]. According to their characteristics of being extremely www.aging-us.com stable and abundant and having cancer-specific expression profiles, the study of circular RNAs has 2 main applications [5]. Increasing evidence suggests that circular RNAs play a key role in regulating bladder cancer progression. Conclusions: Our study firstly demonstrate that circ5912 regulates mesenchymal-to epithelial transition pathway to suppress bladder cancer progression and propose new therapeutic targets and biomarkers for bladder cancer. RNA pulldown assays and florescent in situ hybridization were applied for mechanistic analysis
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