Abstract
BackgroundIncreasing evidences indicate that circular RNAs exert critical function in regulating bladder cancer progression. However, the expressive patterns and roles of circular RNAs in bladder cancer remain less investigated.MethodscircRIP2 was identified and evaluated by RNA-sequencing and qPCR; in vitro effects of circRIP2 were determined by CCK8, clone forming, wound healing and trans-well assays; while mice subcutaneous tumor model was designed for in vivo analysis. Western blot, RNA pulldown assay, miRNA capture and dual luciferase assessment were applied for mechanistic studies.ResultscircRIP2 was identified as a conserved and dramatically repressed circular RNA in bladder cancer. Patients that displayed higher circRIP2 expression negatively associate with the grade, stage, metastasis as well as outcome of bladder cancer. In vitro and in vivo studies suggest that circRIP2 enables to promote bladder cancer progression via inducing EMT. Regarding the mechanism, we performed RNA-sequencing analysis, RNA pulldown with biotin-labeled circRIP2-specific probe, dual luciferase reporter assay. It was found that circRIP2 enables to sponge miR-1305 to elevate Tgf-β2 in bladder cancer, and inducing EMT via Tgf-β2/smad3 pathway. Blocking Tgf-β2 in bladder cancer deprives circRIP2 induced cancer progression and EMT.ConclusionsTaken together, our study provides the first evidence that circRIP2 expresses differentially in bladder cancer and negatively along with the cancer progression; effective circRIP2 activity accelerates bladder cancer progression via inducing EMT by activating miR-1305/Tgf-β2/smad3 pathway. The research implies that circRIP2 might be a potential biomarker and therapeutic target for bladder cancer patients.
Highlights
The risk of bladder cancer in affecting men’s health ranks the top one in Chinese urological cancer [1]
Our study provides the first evidence that circRIP2 expresses differentially in bladder cancer and negatively predicts cancer progression; effective circRIP2 activity accelerates bladder cancer progression via inducing EpithelialMesenchymal Transition (EMT) by activating miR-1305/Tgf-β2/smad3 pathway
These results suggested that circRIP2 is circular RNA
Summary
The risk of bladder cancer in affecting men’s health ranks the top one in Chinese urological cancer [1]. Because of lack of diagnostic and therapeutic approaches, most patients are diagnosed as high grade tumor as soon as they are found [3]. Facing with those circular RNAs are a new class of spliced RNA form and have been identified to play an ultimate role in cancer biology. Researches of circular RNAs are divided into 2 parts, one is to identify its carcinogenic role, the other is to prove its application as a biomarker [5]. The expressive patterns and roles of circular RNAs in bladder cancer remain less investigated
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