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CircHIPK3 sponges miR-558 to suppress heparanase expression in bladder cancer cells
Yawei Li1, Fuxin Zheng1, Xingyuan Xiao1
1Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Abstract:
Increasing evidences suggest that circular RNAs (circRNAs) exert crucial functions in regulating gene expression. In this study, we perform RNA-seq and identify 6,154 distinct circRNAs from human bladder cancer and normal bladder tissues. We find that hundreds of circRNAs are significantly dysregulated in human bladder cancer tissues. We further show that circHIPK3, also named bladder cancer-related circular RNA-2 (BCRC-2), is significantly down-regulated in bladder cancer tissues and cell lines, and negatively correlates with bladder cancer grade, invasion as well as lymph node metastasis, respectively. Over-expression of circHIPK3 effectively inhibits migration, invasion, and angiogenesis of bladder cancer cells in vitro and suppresses bladder cancer growth and metastasis in vivo Mechanistic studies reveal that circHIPK3 contains two critical binding sites for the microRNA miR-558 and can abundantly sponge miR-558 to suppress the expression of heparanase (HPSE). Taken together, our findings provide evidence that circRNAs act as "microRNA sponges", and suggest a new therapeutic target for the treatment of bladder cancer.
Insights
Circular RNAs (circRNAs) regulate gene expression. This study identifies circHIPK3 as a tumor suppressor in bladder cancer by sponging miR-558, offering a potential new therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are increasingly recognized for their roles in gene expression regulation.
- Dysregulation of circRNAs is implicated in various diseases, including cancer.
Purpose of the Study:
- To identify and characterize circRNAs in human bladder cancer.
- To investigate the function of circHIPK3 in bladder cancer progression and its underlying mechanisms.
Main Methods:
- RNA sequencing (RNA-seq) was employed to identify circRNAs in bladder cancer and normal tissues.
- Functional assays (in vitro and in vivo) were performed to assess the role of circHIPK3.
- Mechanism studies involved investigating the interaction between circHIPK3, miR-558, and heparanase (HPSE).
Main Results:
- 6,154 distinct circRNAs were identified, with hundreds found to be significantly dysregulated in bladder cancer.
- circHIPK3 (BCRC-2) was significantly down-regulated in bladder cancer and correlated negatively with tumor grade, invasion, and metastasis.
- Over-expression of circHIPK3 inhibited bladder cancer cell migration, invasion, angiogenesis, and suppressed tumor growth and metastasis in vivo.
- circHIPK3 acts as a miR-558 sponge, suppressing HPSE expression.
Conclusions:
- circRNAs play crucial roles in bladder cancer.
- circHIPK3 functions as a tumor suppressor by sponging miR-558 and inhibiting HPSE.
- circHIPK3 represents a potential novel therapeutic target for bladder cancer treatment.
