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Updated: Oct 15, 2025

Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
A Novel ZNF304/miR-183-5p/FOXO4 Pathway Regulates Cell Proliferation in Clear Cell Renal Carcinoma
Li-Xin Ren1, Bo-Wen Zeng2, Meng Zhu1
1Department of Urology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Abstract:
Zinc-finger protein 304 (ZNF304) plays a critical role in silencing genes through transcription, regulating cell survival, proliferation, apoptosis, and differentiation during development. However, the roles of transcription factor ZNF304 and its clinical significance in clear cell renal carcinoma (ccRCC) remain unclear. In this study, we found that the expression of ZNF304 was downregulated in ccRCC tissues. Lower levels of ZNF304 were correlated with poor survival. Downregulation of ZNF304 promoted ccRCC cell growth in vitro, whereas overexpression of ZNF304 inhibited growth. Our results indicated that miR-183-5p/FOXO4 mediated ZNF304 regulation of cell growth. Interestingly, we revealed that ZNF304 promoted FOXO4 expression in ccRCC cells. Mechanistically, ZNF304 binds to miR-183 promoter and inhibits miR-183-5p transcription. Furthermore, the expression of miR-183-5p wes increased in ccRCC tissues, and the upregulation of miR-183-5p was related to the poor prognosis of ccRCC patients. miR-183-5p upregulation repressed the expression of FOXO4 and promoted ccRCC progression. These results demonstrated that ZNF304/miR-183-5p/FOXO4 axis played essential role in promoting ccRCC progression, which suggests that disruption of this axis may be a potential therapeutic target in ccRCC.
Insights
Zinc-finger protein 304 (ZNF304) is downregulated in clear cell renal carcinoma (ccRCC), promoting tumor growth. Targeting the ZNF304/miR-183-5p/FOXO4 axis may offer new ccRCC therapies.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- Zinc-finger protein 304 (ZNF304) is crucial for gene silencing and cellular processes.
- The role and clinical significance of ZNF304 in clear cell renal carcinoma (ccRCC) are not well understood.
Purpose of the Study:
- To investigate the role of ZNF304 in ccRCC progression.
- To elucidate the molecular mechanism underlying ZNF304's function in ccRCC.
Main Methods:
- Analysis of ZNF304 expression in ccRCC tissues.
- In vitro studies on ccRCC cell growth.
- Investigation of the miR-183-5p/FOXO4 pathway.
- ZNF304 binding to the miR-183 promoter was assessed.
Main Results:
- ZNF304 expression is downregulated in ccRCC and correlates with poor survival.
- Reduced ZNF304 promotes ccRCC cell growth; its overexpression inhibits growth.
- The ZNF304/miR-183-5p/FOXO4 axis regulates ccRCC cell growth, with ZNF304 inhibiting miR-183-5p transcription and promoting FOXO4 expression.
- miR-183-5p is upregulated in ccRCC, associated with poor prognosis, and promotes ccRCC progression by repressing FOXO4.
Conclusions:
- The ZNF304/miR-183-5p/FOXO4 axis is a key driver of ccRCC progression.
- This axis represents a potential therapeutic target for ccRCC treatment.
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