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Published on: March 30, 2019
miR-204 Negatively Regulates Cell Growth And Metastasis By Targeting ROBO4 In Human Bladder Cancer
1Department of Urology, Henan University Huaihe Hospital, Kaifeng 475000, People's Republic of China.
Background:
MicroRNAs (miRNAs) are well characterized for their important roles in human cancers by influencing various aspects of malignancy. Till now, the function and mechanism of miR-204, a tumor suppressor in several cancers, remain unclear in bladder cancer (BC). Here, we intend to explore its roles in BC progression.
Methods:
qRT-PCR was applied to determine miR-204 and ROBO4 expression in BC tissues and cell lines. miR-204 expression with clinicopathological features was analyzed. The impacts of miR-204 on BC cell growth and metastasis in vitro were evaluated by both loss-of-function and gain-of-function assays (CCK-8, crystal violet staining, wound healing and transwell assays). Furthermore, qRT-PCR, Western blot and luciferase reporter assays were used to validate the targeting of ROBO4 by miR-204. Finally, linear regression was performed to analyze the correlation of miR-204 and ROBO4 in BC tissues.
Results:
Expression of miR-204 was markedly decreased in BC tissues and cell lines were compared with respective controls. Low miR-204 expression was associated with positive advanced T stage and lymph node metastasis. Cellular function studies revealed that miR-204 inhibited BC cell growth, migration and invasion. Mechanistic exploration found that miR-204 directly targeted ROBO4. Rescue assays indicated that ROBO4 restoration could reverse the antitumor effects of miR-204 in BC. Finally, ROBO4 was significantly correlated with miR-204 levels inversely.
Conclusion:
miR-204 might serve as a tumor suppressor in BC by targeting ROBO4.
Insights
MicroRNA-204 (miR-204) acts as a tumor suppressor in bladder cancer (BC) by inhibiting cell growth and metastasis. It targets ROBO4, suggesting potential therapeutic applications for BC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) regulate gene expression and are implicated in various human cancers.
- The specific role of miR-204, a known tumor suppressor, in bladder cancer (BC) progression remains largely uncharacterized.
- Understanding miR-204's function in BC is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the role and mechanism of miR-204 in bladder cancer progression.
- To determine if miR-204 functions as a tumor suppressor in BC.
- To identify potential downstream targets of miR-204 in BC.
Main Methods:
- Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to assess miR-204 and ROBO4 expression.
- In vitro assays (CCK-8, crystal violet staining, wound healing, Transwell) to evaluate the impact of miR-204 on BC cell proliferation, migration, and invasion.
- Western blot and luciferase reporter assays to confirm the direct targeting of ROBO4 by miR-204.
- Correlation analysis between miR-204 and ROBO4 expression in BC tissues.
Main Results:
- miR-204 expression was significantly downregulated in BC tissues and cell lines compared to normal controls.
- Low miR-204 levels correlated with advanced tumor stage and lymph node metastasis.
- Overexpression of miR-204 suppressed BC cell growth, migration, and invasion in vitro.
- miR-204 was found to directly target ROBO4, and its restoration reversed the anti-tumor effects.
- A significant inverse correlation was observed between miR-204 and ROBO4 expression in BC tissues.
Conclusions:
- miR-204 functions as a tumor suppressor in bladder cancer.
- The tumor-suppressive activity of miR-204 in BC is mediated through the direct targeting of ROBO4.
- miR-204 represents a potential diagnostic biomarker and therapeutic target for bladder cancer.
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