期刊
CELL DEATH DISCOVERY
卷 7, 期 1, 页码 -出版社
SPRINGERNATURE
DOI: 10.1038/s41420-021-00682-y
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资金
- Shanghai Science and Technology Development Foundation [17JC1400904]
The study found that high expression of KDM4D in ccRCC is associated with lower overall survival rates and higher pathological grades, promoting tumor growth by influencing genes related to vessel morphogenesis. It was also revealed that KDM4D can interact directly with the JAG1 gene promoter to advance tumor angiogenesis.
Kidney cancer, especially clear cell renal cell carcinoma (ccRCC), is one of the representative genitourinary tumors. Investigation of underlying mechanisms of ccRCC development is crucial for patient management. Histone demethylase KDM4D has been reported to be responsible for development of a variety of cancers. However, the role of KDM4D in ccRCC progression is poorly understood. In our study, we performed immunohistochemistry analysis of tissue microarrays first, and results showed that high expression level of KDM4D is connected with advanced Fuhrman grade (p = 0.0118) and lower overall survival (p = 0.0020). Then, we revealed that KDM4D can prompt ccRCC development by interacting with genes related to vessel morphogenesis. Finally, we disclosed that KDM4D directly interacts with JAG1 promoter and advances tumor angiogenesis by upregulating VEGFR-3 and antagonizing notch signaling. The results of our study indicate that KDM4D would be a potential prognostic marker and therapeutic target for ccRCC patients.
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