The circINTS4/miR-146b/CARMA3 axis promotes tumorigenesis in bladder cancer
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Updated: Jan 29, 2026

Culture of Bladder Cancer Organoids as Precision Medicine Tools
Published on: December 28, 2021
Xiaotong Zhang1, Xi Liu1, Zhifei Jing1
1Department of Urology, The First Hospital of China Medical University, Shenyang, Liaoning, 110001, China.
Abstract:
Accumulating evidence shows that circular RNAs (circRNAs) function as microRNA sponges that regulate gene expression in the progression of human cancers. However, the roles of circRNAs and functional miRNA sponges in bladder cancer (BC) remain largely unknown. In the present study, we applied bioinformatics methods and hypothesised that miR-146b may target the 3'-untranslated region (UTR) of CARMA3 mRNA and circINTS4 may serve as a sponge for miR-146b in BC tumorigenesis. Expression of circINTS4 was significantly increased in miR-146b-downregulated BC tissues and cell lines compared to adjacent normal tissues. Furthermore, circINTS4 was found to control multiple pathological processes, including cell proliferation and migration, the cell cycle and apoptosis. Regarding the mechanism, circINTS4 directly bound to miR-146b to inhibit its activity of targeting the 3'-UTR of CARMA3 mRNA. In addition, circINTS4 could activate the NF-kB signalling pathway and suppress the P38 MAPK signalling pathway in a CARMA3-mediated manner in BC cells. In summary, the circINTS4/miR-146b/CARMA3 axis might serve as a promising therapeutic target for BC intervention.
Insights
Circular RNAs (circRNAs) regulate gene expression in cancer. This study identifies circINTS4 as a microRNA sponge for miR-146b, impacting bladder cancer (BC) progression by targeting CARMA3 and influencing key signaling pathways.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are increasingly recognized for their roles in gene regulation within human cancers.
- The specific functions of circRNAs and their microRNA (miRNA) sponge activities in bladder cancer (BC) are not well understood.
Purpose of the Study:
- To investigate the role of circINTS4 as a potential miRNA sponge for miR-146b in the context of bladder cancer (BC) tumorigenesis.
- To elucidate the molecular mechanism by which circINTS4 influences BC progression through the miR-146b/CARMA3 axis.
Main Methods:
- Bioinformatic analysis to identify potential circRNA-miRNA interactions.
- Quantitative expression analysis of circINTS4 and miR-146b in BC tissues and cell lines.
- Functional assays to assess the impact of circINTS4 on cell proliferation, migration, cell cycle, and apoptosis.
- Mechanism studies involving direct binding assays and pathway analysis (NF-kB, P38 MAPK).
Main Results:
- CircINTS4 expression was significantly elevated in BC tissues and cell lines with low miR-146b levels.
- CircINTS4 demonstrated regulatory control over BC cell proliferation, migration, cell cycle, and apoptosis.
- CircINTS4 directly sponged miR-146b, thereby inhibiting miR-146b's targeting of the CARMA3 3'-UTR.
- The circINTS4/miR-146b/CARMA3 interaction modulated the NF-kB and P38 MAPK signaling pathways in BC cells.
Conclusions:
- The circINTS4/miR-146b/CARMA3 regulatory axis plays a significant role in bladder cancer (BC) pathogenesis.
- This axis represents a potential novel therapeutic target for bladder cancer (BC) intervention.
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