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Modeling Spontaneous Metastatic Renal Cell Carcinoma mRCC in Mice Following Nephrectomy
Published on: April 29, 2014
MicroRNA-10b Promotes Apoptosis via JNK Pathway in Clear Cell Renal Cell Carcinoma
Jianyang Qin1, Jia Zhou2, Ling Teng3
1Department of Nephrology, Affiliated Second Hospital, Mudanjiang Medical College, Mudangjiang, China.
Background/Aims:
To investigate the downregulation of microRNA (miR)-10b in clear cell renal cell carcinoma (ccRCC) and its mechanistic involvement in tumourigenesis.
Methods:
The relative expression of miR-10b in ccRCC samples were determined by real-time PCR. Exogenous expression and knockdown of endogenous miR-10b were performed by transfection with indicated plasmids into 786-0 cells. Cell proliferation was evaluated using Cell Counting Kit-8 assay. Cell apoptosis was analyzed by Annexin V/propidium iodide staining. MAPK pathway activation was detected by western blotting with indicated antibodies.
Results:
We confirmed the downregulation of miR-10b in ccRCC tumour. The forced expression of miR-10b inhibited cell proliferation in 786-0 cells. Moreover, miR-10b stimulated apoptosis in 786-0 cells, which was abrogated by specific miR-10b inhibitor. We further elucidated that the apoptosis induction was mediated by the JNK pathway activation. We consolidated this observation by combinational treatment with JNK specific inhibitor, which was shown to completely impede miR-10b elicited apoptosis.
Conclusion:
We suggested a tumour suppressor function of miR-10b in tumourigenesis of ccRCC via proliferation suppression and apoptosis induction, and the latter was mediated by the JNK pathway activation.
Insights
MicroRNA (miR)-10b is downregulated in clear cell renal cell carcinoma (ccRCC). Restoring miR-10b suppresses tumor growth and induces apoptosis via the JNK pathway, suggesting a tumor suppressor role.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Clear cell renal cell carcinoma (ccRCC) is a significant health concern.
- The role of microRNAs (miRNAs) in ccRCC pathogenesis is an active area of research.
- Specific miRNA dysregulation, like miR-10b downregulation, may contribute to ccRCC development.
Purpose of the Study:
- To investigate the downregulation of microRNA (miR)-10b in clear cell renal cell carcinoma (ccRCC).
- To elucidate the mechanistic involvement of miR-10b in ccRCC tumorigenesis.
- To determine the impact of miR-10b on cell proliferation and apoptosis in ccRCC.
Main Methods:
- Real-time PCR was used to determine miR-10b expression levels in ccRCC samples.
- miR-10b expression and knockdown were achieved using plasmid transfection in 786-0 cells.
- Cell proliferation, apoptosis, and MAPK/JNK pathway activation were assessed using CCK-8 assay, Annexin V/PI staining, and Western blotting, respectively.
Main Results:
- miR-10b was confirmed to be downregulated in ccRCC tumors.
- Forced expression of miR-10b inhibited cell proliferation and induced apoptosis in 786-0 cells.
- Apoptosis induction by miR-10b was mediated by the activation of the JNK pathway.
Conclusions:
- miR-10b functions as a tumor suppressor in ccRCC.
- miR-10b inhibits ccRCC cell proliferation and promotes apoptosis.
- The pro-apoptotic effect of miR-10b in ccRCC is dependent on JNK pathway activation.
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