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组蛋白去甲基化酶 KDM4B 促进高级别透明细胞肾细胞癌的发生发展,与拷贝数变异和细胞周期进程相关。

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

机构信息

Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

出版信息

Epigenetics. 2023 Dec;18(1):2192319. doi: 10.1080/15592294.2023.2192319.

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 . 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 , as well as tumour growth and metastasis . 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.

摘要

高级肾细胞癌 (RCC) 威胁着患者的生存。表观遗传重塑是肾癌的发病机制。组蛋白去甲基化酶 4B (KDM4B) 通过多种途径在许多癌症中过表达。然而,KDM4B 在透明细胞肾细胞癌中的作用尚未阐明。首先通过分析公共数据库验证了 KDM4B 的差异表达。通过 Western blot 和免疫组织化学染色进一步分析了 KDM4B 在新鲜组织和病理切片中的表达。还建立了 KDM4B 过表达和敲低细胞系。使用细胞计数试剂盒-8 (CCK-8) 测定法检测细胞生长。进行 Transwell 测定以评估细胞迁移。使用异种移植评估肿瘤生长和转移。最后,根据单细胞 RNA 测序数据评估了 KDM4B 表达水平与拷贝数变异 (CNV) 和细胞周期阶段的相关性。KDM4B 在肿瘤组织中的表达水平高于相邻正常组织。高水平的 KDM4B 与较差的病理特征和较差的预后相关。KDM4B 还促进细胞增殖和迁移,以及肿瘤生长和转移。高 KDM4B 表达的肿瘤细胞表现出更高的 CNV 水平和更多处于 G1/S 转换期的细胞比例。我们的结果证实 KDM4B 促进了透明细胞肾细胞癌的进展,与预后不良相关,并且可能与高水平的 CNV 和细胞周期进展有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41d6/10038057/f8dc38067e01/KEPI_A_2192319_F0001_OC.jpg

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