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The circ_0004463/miR-380-3p/FOXO1 axis modulates mitochondrial respiration and bladder cancer cell apoptosis
Shuiqing Wu1, Huanghao Deng1, Haiqing He1
1Department of Urology, The Second Xiangya Hospital, Central South University , Changsha, Hunan Province, People's Republic of China.
Abstract:
Bladder cancer is one of the most commonly diagnosed and fatal malignancies of the urinary tract. Noncoding RNAs have been reported to be new biomarkers and effective treatment targets for bladder cancer. In the present study, we identified a novel bladder cancer-related circRNA-miRNA-mRNA network, the circ_0004463/miR-380-3p/FOXO1 axis. circ_0004463 is significantly downregulated, whereas miR-380-3p is upregulated in bladder carcinoma tissue samples and cells. circ_0004463 acts as a tumor suppressor by inhibiting bladder cancer cell proliferation. Genes that negatively correlated with miR-380-3p and genes that miR-380-3p might target are enriched in mitochondrial respiration chain-related pathways. miR-380-3p promotes the proliferation of bladder cancer cells and mitochondrial respiration by acting as an oncogenic miRNA. circ_0004463 competes with FOXO1 for miR-380-3p binding to counteract miR-380-3p-mediated repression of FOXO1. Circ_0004463 overexpression inhibits cancer cell proliferation and mitochondrial respiration in bladder cancer cell lines, while miR-380-3p overexpression dramatically reverses the roles of circ_0004463 overexpression. In conclusion, the circ_0004463/miR-380-3p/FOXO1 axis could regulate mitochondrial respiration and bladder cancer cell apoptosis via FOXO1 signaling.
Insights
This study identifies the circ_0004463/miR-380-3p/FOXO1 axis as a key regulator in bladder cancer. Circ_0004463 acts as a tumor suppressor, inhibiting cancer cell proliferation and mitochondrial respiration.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Bladder cancer is a prevalent and lethal malignancy.
- Noncoding RNAs show promise as bladder cancer biomarkers and therapeutic targets.
Purpose of the Study:
- To elucidate a novel bladder cancer-associated circRNA-miRNA-mRNA regulatory network.
- To investigate the role of the circ_0004463/miR-380-3p/FOXO1 axis in bladder cancer progression.
Main Methods:
- Analysis of circRNA, miRNA, and mRNA expression in bladder cancer tissues and cells.
- Investigation of the functional roles of circ_0004463 and miR-380-3p in bladder cancer cell lines.
- Luciferase reporter assays to confirm direct targeting interactions.
Main Results:
- Circ_0004463 was significantly downregulated, while miR-380-3p was upregulated in bladder cancer.
- Circ_0004463 suppressed bladder cancer cell proliferation and mitochondrial respiration.
- miR-380-3p promoted proliferation and mitochondrial respiration, acting as an oncogenic miRNA.
- The circ_0004463/miR-380-3p/FOXO1 axis regulates bladder cancer cell apoptosis and mitochondrial respiration.
Conclusions:
- The circ_0004463/miR-380-3p/FOXO1 axis is a critical regulatory pathway in bladder cancer.
- Circ_0004463 functions as a tumor suppressor by targeting the miR-380-3p/FOXO1 pathway.
- This axis represents a potential therapeutic target for bladder cancer treatment.
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