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miR-135a-5p exerts tumor-suppressive effects in 769P renal carcinoma cells through the TFAP2A/KRT8 signaling axis
Delong Xie1, Jizhe Zhou1, Yueyue Guo1
1College of Basic Medical Sciences, Youjiang Medical University for Nationalities, Baise, Guangxi, China.
Abstract:
The oncogenic roles of microRNAs have been extensively documented across various cancer types. In the present study, we aimed to investigate the functional impact of miR-135a-5p on the clear cell renal cell carcinoma (ccRCC) cell line 769P. Through weighted gene co-expression network analysis (WGCNA), we identified a significant association between miR-135a-5p and ccRCC progression. Furthermore, miR-135a-5p expression was downregulated in both ccRCC tissues and cell lines. Functional assays demonstrated that miR-135a-5p inhibits the progression of 769P cells. Mechanistically, miR-135a-5p directly binds to the 3' untranslated region (3'UTR) of TFAP2A, reducing its mRNA stability. In turn, TFAP2A binds to the promoter region of KRT8 and activates its transcription, thereby mediating the inhibitory effect of miR-135a-5p on 769P cell progression. In conclusion, our findings provide evidence that miR-135a-5p suppresses ccRCC progression in 769P cells through the TFAP2A/KRT8 axis, highlighting its potential as a therapeutic target for ccRCC.
Insights
MicroRNA miR-135a-5p suppresses clear cell renal cell carcinoma (ccRCC) progression by targeting TFAP2A and KRT8. This finding highlights miR-135a-5p as a potential therapeutic target for ccRCC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) play crucial roles in cancer development.
- The specific function of miR-135a-5p in clear cell renal cell carcinoma (ccRCC) requires further investigation.
Purpose of the Study:
- To investigate the role of miR-135a-5p in ccRCC progression.
- To elucidate the molecular mechanism underlying miR-135a-5p's function in ccRCC.
Main Methods:
- Weighted gene co-expression network analysis (WGCNA) to identify gene associations.
- Expression analysis in ccRCC tissues and cell lines.
- Functional assays to assess cell progression.
- Luciferase reporter assays to confirm direct binding to TFAP2A 3'UTR.
Main Results:
- miR-135a-5p expression is downregulated in ccRCC.
- miR-135a-5p inhibits ccRCC cell line 769P progression.
- miR-135a-5p directly targets TFAP2A, reducing its mRNA stability.
- TFAP2A activates KRT8 transcription, mediating miR-135a-5p's inhibitory effect.
Conclusions:
- miR-135a-5p acts as a tumor suppressor in ccRCC.
- The miR-135a-5p/TFAP2A/KRT8 axis is a key pathway in ccRCC progression.
- miR-135a-5p represents a potential therapeutic target for ccRCC.
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