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Published on: April 7, 2017
Micro-RNA378a-3p Induces Apoptosis in Sarcomatoid Renal Cell Carcinoma and Regulates POLR2A and RUNX2 Expression
Wen-Hui Weng1, Kai-Jie Yu2,3, Ju-Wen Jhan2
1Department of Chemical Engineering and Biotechnology and Graduate Institute of Biochemical and Biomedical Engineering, National Taipei University of Technology, Taipei, Taiwan, R.O.C.; wendywwh@ntut.edu.tw.
Background/Aim:
Sarcomatoid renal cell carcinoma (sRCC) is an aggressive subtype of RCC. In the current study, we investigated whether the POLR2A and RUNX2 genes are involved in RCC-related signaling pathway and associated with miR-378.
Materials And Methods:
Thirteen formalin-fixed and paraffin-embedded RCC samples were collected. Three software programs were used to predict the potential gene regulation in RCC by miR-378 and immunohistochemistry analysis was applied to confirm the expression of targeted proteins in FFPE samples. MicroRNA-378 transfection, analysis of mRNA and protein expression via Western Blotting and cell apoptosis analysis via flow cytometry for POLR2A and RUNX2 were further studied in four renal cell carcinoma cell lines.
Results:
Both the mRNA and protein expression levels of POLR2A and RUNX2 in sRCC cell lines and were significantly higher than those in other subtypes of RCC, and similar results were obtained in clinical samples (p<0.01). Second, overexpression of miR-378 significantly suppressed the expression of POLR2A and RUNX2 in sRCC cells (p<0.01) and enhanced apoptosis (p<0.05).
Conclusion:
miR-378 significantly inhibits the expression of POLR2A and RUNX2 in sRCC and further promotes apoptosis of sRCC cells. We speculated that the apoptosis mechanism in sRCC occurs via regulation of the ERK2 and PI3K/AKT pathways, which might distinguish it from other subtypes of RCC.
Insights
MicroRNA-378 (miR-378) inhibits POLR2A and RUNX2 gene expression in sarcomatoid renal cell carcinoma (sRCC), promoting cancer cell apoptosis. This finding offers potential therapeutic targets for aggressive sRCC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Sarcomatoid renal cell carcinoma (sRCC) is an aggressive cancer subtype.
- The roles of POLR2A and RUNX2 genes in RCC and their association with miR-378 remain unclear.
Purpose of the Study:
- Investigate the involvement of POLR2A and RUNX2 in RCC signaling pathways.
- Determine the association between POLR2A, RUNX2, and miR-378 in sRCC.
- Explore the therapeutic potential of targeting these molecules in sRCC.
Main Methods:
- Analyzed 13 formalin-fixed, paraffin-embedded RCC samples.
- Utilized software to predict miR-378 gene regulation in RCC.
- Performed immunohistochemistry, Western Blotting, and flow cytometry on RCC cell lines and samples.
- Conducted microRNA-378 transfection experiments.
Main Results:
- POLR2A and RUNX2 mRNA and protein levels were significantly higher in sRCC compared to other RCC subtypes.
- Overexpression of miR-378 significantly suppressed POLR2A and RUNX2 expression in sRCC cells.
- miR-378 overexpression enhanced apoptosis in sRCC cells.
Conclusions:
- miR-378 inhibits POLR2A and RUNX2 expression in sRCC, promoting apoptosis.
- The observed apoptosis mechanism in sRCC may involve ERK2 and PI3K/AKT pathways.
- These findings suggest miR-378 as a potential therapeutic target for sRCC.
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