Related Experiment Video
Updated: Dec 16, 2025
Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer
Published on: August 2, 2024
Circular RNA FOXO3 Suppresses Bladder Cancer Progression and Metastasis by Regulating MiR-9-5p/TGFBR2
Yongxiang Li1,2, Liang Qiao2, Yuanwei Zang1
1Department of Urology, Qilu Hospital of Shandong University, Jinan 250012, People's Republic of China.
Background:
Increasing evidence indicates that the dysregulation of circular RNAs (circRNAs) plays important roles in tumor progressions.
Methods:
In this study, we first analyzed circ-FOXO3 level in bladder cancers (BCs), and then BC cell lines were transfected with circ-FOXO3 expression vector, and cell proliferation, migration, and invasion abilities were analyzed. We also used bioinformatics tools to predict potential-binding miRNAs for circ-FOXO3, and luciferase reporter assay was used for the verification of binding miRNAs. For the further study, we analyzed potential downstream-binding mRNA for miRNA, and cell proliferation, migration and invasion abilities of it were also studied.
Results:
We found that circ-FOXO3 was significantly down-regulated in bladder cancer (BC) tissues compared to normal bladder tissues. We also found that circ-FOXO3 overexpression inhibited cell proliferation, migration and invasion in BC cell lines. Moreover, we demonstrated that TGFBR2 was regulated by circ-FOXO3 through sponging miR-9-5p, the knockdown of TGFBR2 or the overexpression of miR-9-5p all related to the increased BC cell proliferation, migration, and invasion.
Discussion:
In summary, our data showed that circ-FOXO3 was significantly down-regulated in bladder cancers. circ-FOXO3 overexpression inhibits BC cell progression and metastasis. Furthermore, circ-FOXO3 regulates TGFBR2 expression through sponging miR-9-5p in BC cell lines.
Insights
Circular RNAs (circRNAs) are implicated in tumor progression. This study found circ-FOXO3 is downregulated in bladder cancer and inhibits tumor growth and metastasis by regulating TGFBR2 via miR-9-5p.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are increasingly recognized for their roles in cancer development.
- Dysregulation of circRNAs is a hallmark of various tumor progressions.
Purpose of the Study:
- To investigate the role of circ-FOXO3 in bladder cancer (BC).
- To elucidate the molecular mechanism by which circ-FOXO3 affects BC progression.
Main Methods:
- Quantification of circ-FOXO3 levels in BC tissues and cell lines.
- Functional assays (proliferation, migration, invasion) following circ-FOXO3 overexpression.
- Bioinformatic prediction and luciferase reporter assays to identify and validate miRNA interactions.
- Analysis of downstream target gene (TGFBR2) regulation and its functional impact.
Main Results:
- circ-FOXO3 was significantly downregulated in bladder cancer tissues compared to normal tissues.
- Overexpression of circ-FOXO3 suppressed proliferation, migration, and invasion of BC cell lines.
- circ-FOXO3 acts as a sponge for miR-9-5p, thereby inhibiting the expression of its target gene, TGFBR2.
- TGFBR2 knockdown or miR-9-5p overexpression mimicked the pro-tumorigenic effects observed in BC.
Conclusions:
- circ-FOXO3 is downregulated in bladder cancer and functions as a tumor suppressor.
- circ-FOXO3 inhibits BC cell progression and metastasis.
- The circ-FOXO3/miR-9-5p/TGFBR2 axis is a critical regulatory pathway in bladder cancer.
Related Concept Videos
01:22MicroRNAs
01:22MicroRNAs
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
02:15Experimental RNAi