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Published on: January 22, 2013
miR-33a inhibits cell growth in renal cancer by downregulation of MDM4 expression
Kehua Jiang1, Fa Sun1, Jianguo Zhu1
1Department of Urology, Guizhou Provincial People's Hospital, Guiyang, China.
Background:
MicroRNA-33a (miR-33a) plays the role of the tumor suppressor gene by regulating the expression level of downstream genes. However, the effects of miR-33a in renal cell cancer (RCC) remain unknown. Our study was designed to investigate the expression level and potential function of miR-33a in RCC.
Methods:
RT-qPCR was applied to measure the levels of miR-33a in RCC tissues and cell lines. Western blotting and luciferase reporter assay were used to detect the relationship between miR-33a and Mouse double minute 4 (MDM4) in RCC cells. CCK-8 and flow cytometry were applied to detected cell viability and cell cycle. Animal models and TUNEL assay were applied to detect the effect of miR-33a on the growth of RCC and cell apoptosis.
Results:
We found that the levels of miR-33a were significantly decreased in RCC tissues and cell lines. Moreover, the low expression of miR-33a in RCC patients indicated a shorter overall survival (OS). Notably, MDM4 as a direct target of miR-33a in RCC, the expression level of MDM4 was significantly increased in RCC cells group than the control group. Furthermore, miR-33a overexpression significantly inhibited RCC cells growth than the control group, while the inhibitory effects of miR-33a were reversed upon the overexpression of MDM4. Luciferase reporter assays showed that there was a direct interaction between miR-33a and 3' UTR of MDM4 mRNA. In vivo, tumor volumes and weight were significantly decreased in the transfected miR-33a mimics group than the control group.
Conclusion:
Taken together, our study indicates that miR-33a inhibits RCC cell growth by targeting MDM4.
Insights
MicroRNA-33a (miR-33a) is decreased in renal cell cancer (RCC), suppressing tumor growth by targeting MDM4. Low miR-33a levels correlate with shorter survival in RCC patients.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- MicroRNA-33a (miR-33a) functions as a tumor suppressor by regulating downstream gene expression.
- The specific role of miR-33a in renal cell cancer (RCC) has not been previously elucidated.
- This study investigates the expression and function of miR-33a in the context of RCC.
Purpose of the Study:
- To determine the expression levels of miR-33a in RCC tissues and cell lines.
- To investigate the functional role of miR-33a in regulating RCC cell growth and apoptosis.
- To identify the downstream target(s) of miR-33a in RCC.
Main Methods:
- Quantitative reverse transcription polymerase chain reaction (RT-qPCR) for miR-33a expression analysis.
- Western blotting and luciferase reporter assays to confirm miR-33a targeting of MDM4.
- Cell Counting Kit-8 (CCK-8), flow cytometry, and in vivo animal models to assess cellular proliferation, cell cycle, apoptosis, and tumor growth.
Main Results:
- miR-33a expression was significantly downregulated in RCC tissues and cell lines.
- Lower miR-33a expression correlated with reduced overall survival in RCC patients.
- MDM4 was identified as a direct target of miR-33a, with its expression inversely correlated to miR-33a levels.
- Overexpression of miR-33a inhibited RCC cell proliferation and induced apoptosis, effects that were reversed by MDM4 overexpression.
- In vivo studies demonstrated that miR-33a mimics significantly reduced tumor volume and weight.
Conclusions:
- miR-33a acts as a tumor suppressor in renal cell cancer.
- The tumor-suppressive function of miR-33a is mediated through the inhibition of its direct target, MDM4.
- Restoring miR-33a levels may represent a potential therapeutic strategy for RCC.
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