Abstract
Circular RNAs (circRNAs) have been identified as crucial regulators of gene expression in human cancer biology. CircZFR is a novel identified circRNA and its effect in bladder cancer remains unclearly. In the present study, we aimed to investigate the role of circZFR in the progression of bladder cancer. First, we demonstrated that the expression of circZFR was higher in bladder cancer tissues and cells compared with adjacent non-tumor tissues and normal bladder epithelial cells. And higher circZFR levels were positively correlated with bladder cancer patients’ pathological T stage, grade, lymphatic metastasis, recurrence, progression-free survival (PFS) and overall survival (OS). Functionally, knockdown of circZFR could significantly prohibit cell growth, migration and invasion, arrest cell cycle as well as promote apoptosis of bladder cancer cells in vitro study. Mechanistically, we observed that circZFR could directly bind to miR-377 as sponge to promote ZEB2 expression in bladder cancer cells. In addition, rescue assays demonstrated that restoration of ZEB2 significantly impaired the suppressive effects of circZFR silencing on bladder cancer cells growth, migration and invasion. Taken together, our results illuminated that circZFR could be a prognostic biomarker in bladder cancer and exerted oncogenic roles through regulating miR-377/ZEB2 axis in bladder cancer, which indicated that circZFR could be a potential therapeutic target for bladder cancer patients treatment.
Highlights
Bladder cancer (BC) is the most prevalent malignancy of the urinary system worldwide, with the highest morbidity and mortality among urinary system tumors in China [1]
The correlation analysis demonstrated that circZFR expression was associated with clinicopathological features including the tumor stage, grade, lymphatic metastasis, recurrence (Table 1)
An increasing number of circRNAs have been identified as one oncogene or tumor suppressor in tumorigenesis of BC [15]
Summary
Bladder cancer (BC) is the most prevalent malignancy of the urinary system worldwide, with the highest morbidity and mortality among urinary system tumors in China [1]. Bladder cancer consists of 75% non-muscle invasive bladder cancer (NMIBC) and 25% muscle-invasive bladder cancer (MIBC) according to the depth of tumor infiltration [2]. Systemic chemotherapy, target-therapy and immunotherapy have greatly advanced the treatment of BC, the overall survival rate remains unsatisfactory due to the high recurrence and distant metastasis [3]. Identifying novel biomarkers and potential therapeutic targets underlying the tumorigenesis and progression of BC is imperative for building up therapy strategies for BC. More and more circRNAs have been identified as endogenous non-coding RNAs through high-throughput sequencing technology in various cell lines and species. A large amount of studies demonstrate that circRNAs exhibit crucial roles, and may be potential biomarkers and therapeutic targets in cancers [7]
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