Histone demethylase KDM4B contributes to advanced clear cell renal carcinoma and association with copy number variations and cell cycle progression

Abstract

Advanced renal cell carcinoma (RCC) poses a threat to patient survival. Epigenetic remodelling is the pathogenesis of renal cancer. Histone demethylase 4B (KDM4B) is overexpressed in many cancers through various pathways. However, the role of KDM4B in clear cell renal carcinoma has not yet been elucidated. The differential expression of KDM4B was first verified by analysing public databases. The expression of KDM4B in fresh tissues and pathology slides was further analysed by western blotting and immunohistochemical staining. KDM4B overexpression and knockdown cell lines were also established. Cell Counting Kit-8 (CCK-8) assay was used to detect cell growth. Transwell assays were performed to assess cell migration. Xenografts were used to evaluate tumour growth and metastasis in vivo. Finally, KDM4B expression levels associated with copy number variation (CNV) and cell cycle stage were evaluated based on single-cell RNA sequencing data. KDM4B was expressed at higher levels in tumour tissues than in the adjacent normal tissues. High levels of KDM4B are associated with worse pathological features and poorer prognosis. KDM4B also promotes cell proliferation and migration in vitro, as well as tumour growth and metastasis in vivo. Tumour cells with high KDM4B expression exhibited higher CNV levels and a greater proportion of cells in the G1/S transition phase. Our results confirm that KDM4B promotes the progression of clear cell renal carcinoma, is correlated with poor prognosis, and may be related to high levels of CNV and cell cycle progression.

Keywords

• renal cancer
• epigenetics
• histone demethylase 4b
• copy number variation
• cell cycle