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Updated: Jun 25, 2025

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
miR-4429 inhibits ccRCC proliferation, migration, and invasion by directly targeting CD274
GuangYi Hong1, YiKun Wu1, ShiYu Huang2
1Guizhou University Medicine College, Guiyang, 550025, Guizhou, China.
Abstract:
Clear cell renal cell carcinoma (ccRCC) is one of the most aggressive urological malignancies and a highly immunogenic cancer. Yet, its pathogenesis is still not fully understood. This study analyzed the role of the miR-320 family in ccRCC using bioinformatics algorithms and a series of in vitro experiments. miR-4429 was found to be significantly down-regulated in ccRCC tissues and cell lines, while overexpression of miR-4429 significantly inhibited renal cancer cell proliferation, migration, and invasion in vitro. In addition, the UALCAN database, immunohistochemistry, and protein blotting results showed that CD274 expression was up-regulated in ccRCC tissues and correlated with higher histologic grading. Dual luciferase assay indicated that CD274 was a direct target of miR-4429. Overexpression of miR-4429 in 786-O, Caki-2 cells significantly inhibited CD274 expression. KEGG results indicated that the potential target function of miR-4429 was associated with the PI3K/AKT signaling pathway, and protein blotting verified the results. In summary, this data shows that miR-4429 targets CD274 and inhibits ccRCC proliferation, migration, and invasion by regulating PI3K/AKT signaling, thus potentially providing a promising therapeutic target and prognostic biomarker for renal cell carcinoma patients.
Insights
MicroRNA-4429 (miR-4429) is downregulated in clear cell renal cell carcinoma (ccRCC). Restoring miR-4429 inhibits ccRCC growth and spread by targeting CD274 and the PI3K/AKT pathway.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Clear cell renal cell carcinoma (ccRCC) is an aggressive cancer with incompletely understood pathogenesis.
- The role of microRNAs, specifically the miR-320 family, in ccRCC requires further elucidation.
Purpose of the Study:
- To investigate the function of miR-4429 in ccRCC.
- To identify the molecular targets and signaling pathways regulated by miR-4429 in ccRCC.
Main Methods:
- Bioinformatic analysis (UALCAN database).
- In vitro experiments including cell proliferation, migration, and invasion assays.
- Immunohistochemistry, protein blotting, dual luciferase assays, and KEGG pathway analysis.
Main Results:
- miR-4429 was significantly downregulated in ccRCC tissues and cell lines.
- Overexpression of miR-4429 suppressed ccRCC cell proliferation, migration, and invasion.
- CD274 was identified as a direct target of miR-4429 and was upregulated in ccRCC.
- miR-4429 regulates the PI3K/AKT signaling pathway.
Conclusions:
- miR-4429 inhibits ccRCC progression by targeting CD274 and modulating the PI3K/AKT pathway.
- miR-4429 holds potential as a therapeutic target and prognostic biomarker for ccRCC.
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