2. Academic Validation
  3. Histone demethylase KDM4D inhibition suppresses renal cancer progression and angiogenesis through JAG1 signaling

Histone demethylase KDM4D inhibition suppresses renal cancer progression and angiogenesis through JAG1 signaling

  • Cell Death Discov. 2021 Oct 11;7(1):284. doi: 10.1038/s41420-021-00682-y.
Hao Yan  # 1,  Liangsong Zhu  # 1,  Jin Zhang 2,  Zongming Lin 3
Affiliations

Affiliations

  • 1 Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
  • 2 Department of Urology, Renji hospital, Shanghai Jiaotong University, Shanghai, China.
  • 3 Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China. [email protected].
  • # Contributed equally.
PMID: 34667158 DOI: 10.1038/s41420-021-00682-y
Abstract

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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