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miR-199a-5p suppresses human bladder cancer cell metastasis by targeting CCR7
Mi Zhou1, Shuai Wang1, Linyi Hu1
1Department of Urology, Zhejiang Provincial People's Hospital, 158 Shangtang Road, Hangzhou, Zhejiang Province, 310014, People's Republic of China.
Background:
C-C chemokine receptor type 7 (CCR7) overexpression correlated with lymphatic metastasis and poor prognosis is a major obstacle to bladder cancer treatment. Recent studies have revealed that miR-199a-5p was significantly abnormal expressed in several solid tumors and functioned as oncogene or tumor suppressor. This study was aimed to further investigate the effects of miR-199a-5p on the cell metastasis mediated by CCR7 in bladder cancer.
Methods:
Quantitative Real Time PCR (qRT-PCR) was firstly performed to identified the expression of miR-199a-5p and CCR7 in human bladder cancer samples and cell lines. Following that, the effects of miR-199a-5p on cell migratory and invasive activities were assessed by wound healing and Matrigel invasion assays, respectively. Finally, luciferase reporter assay and western blot were employed to investigate whether CCR7 could directly interact with miR-199a-5p.
Results:
miR-199a-5p downregulation and CCR7 upregulation were firstly observed in bladder cancer samples and cell lines. In addition, both miR-199a-5p downregulation and CCR7 upregulation were significantly involved in bladder cancer clinicopathological features. Moreover, overexpression of miR-199a-5p could inhibit baldder cancer cell migration and invasion. miR-199a-5p was confirmed to be able to target the 3' untranslated region (UTR) of CCR7 and regulate the expression of CCR7, Matrix metalloproteinases 9 (MMP-9) and Epithelial-Mesenchymal Transition (EMT)-related proteins.
Conclusion:
Our findings added newer insights into the multifaceted role played by miR-199a-5p/CCR7 in bladder cancer, prompting for the first time this miRNA/chemokine axis that regulates cell metastasis. The results strongly supported miR-199a-5p as a potential therapeutic agent and diagnostic marker of bladder cancer.
Insights
MicroRNA-199a-5p (miR-199a-5p) downregulation promotes bladder cancer metastasis by upregulating C-C chemokine receptor type 7 (CCR7). Restoring miR-199a-5p inhibits cancer cell migration and invasion, suggesting its therapeutic potential.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- C-C chemokine receptor type 7 (CCR7) overexpression is linked to lymphatic metastasis and poor prognosis in bladder cancer.
- MicroRNA-199a-5p (miR-199a-5p) expression is altered in various solid tumors, with roles as either an oncogene or tumor suppressor.
Purpose of the Study:
- To investigate the role of miR-199a-5p in bladder cancer cell metastasis.
- To explore the regulatory relationship between miR-199a-5p and CCR7 in bladder cancer.
Main Methods:
- Quantitative Real-Time PCR (qRT-PCR) to assess miR-199a-5p and CCR7 expression.
- Wound healing and Matrigel invasion assays to evaluate cell migration and invasion.
- Luciferase reporter assay and Western blot to confirm direct interaction between miR-199a-5p and CCR7.
Main Results:
- miR-199a-5p was downregulated and CCR7 was upregulated in bladder cancer tissues and cell lines.
- Overexpression of miR-199a-5p inhibited bladder cancer cell migration and invasion.
- miR-199a-5p directly targets CCR7's 3' untranslated region (UTR), regulating CCR7, MMP-9, and EMT-related proteins.
Conclusions:
- The miR-199a-5p/CCR7 axis plays a crucial role in regulating bladder cancer cell metastasis.
- miR-199a-5p demonstrates potential as a therapeutic agent and diagnostic marker for bladder cancer.
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