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ASF1B 是膀胱癌生长和耐药特征相关的重要预后指标。

ASF1B is an essential prognostic indicator linked to the growth and resistance characteristics of bladder cancer.

机构信息

Department of Urology, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, China.

Ministry of Scientific and Technological Innovation, Yantai Hi-tech Industrial Development Zone, Yantai, Shandong 264000, China.

出版信息

Tissue Cell. 2024 Aug;89:102477. doi: 10.1016/j.tice.2024.102477. Epub 2024 Jul 14.

DOI:10.1016/j.tice.2024.102477
PMID:39018712
Abstract

BACKGROUND

Anti-silencing function 1 (ASF1) is a conserved histone H3-H4 chaperone protein. ASF1B (Anti-Silencing Function 1B Histone Chaperone), a paralog of ASF1, is involved in tumor metabolism and growth. The regulatory network of ASF1B in cancer is intricate and remains inadequately explored. The objective of this study was to examine the biological role of ASF1B in bladder cancer (BC).

METHODS

The presence of ASF1B in BC was examined using The Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia (CCLE) databases. In addition, a correlation analysis was performed to evaluate the association between the BC pathway scores and ASF1B. ASF1B expression in BC cells was detected using western blott and RT-PCR. Several investigations were conducted, both within and outside of a living organism, to confirm the involvement of ASF1B in the regulation of biological processes in BC cells.

RESULTS

Our examination of the database indicates that ASF1B exhibits significant expression levels in BC cells and is potentially strongly associated with the growth of BC cells and the repair of DNA. The expression of ASF1B in BC cells was found to be significantly elevated, as indicated by the results of western blot and RT-PCR. The findings of the cell plate cloning test, edu analysis, flow cytometry, and transwell experiments demonstrated that the inhibition of ASF1B greatly impeded the proliferation and migration of BC cells. After establishing drug-resistant BC cell lines in a lab, suppressing ASF1B gene expression led to a notable reduction in BC cells' resistance to cisplatin. Confirmation was achieved by flow cytometry and western blott assays. Our in vivo findings demonstrated that the suppression of ASF1B resulted in an amelioration of the pathological condition, a decrease in resistance to cisplatin, and an inhibition of the growth of BC in mice.

摘要

背景

抗沉默功能 1(ASF1)是一种保守的组蛋白 H3-H4 伴侣蛋白。ASF1B(抗沉默功能 1B 组蛋白伴侣)是 ASF1 的一个同源物,参与肿瘤代谢和生长。ASF1B 在癌症中的调控网络错综复杂,仍未得到充分探索。本研究旨在研究 ASF1B 在膀胱癌(BC)中的生物学作用。

方法

使用癌症基因组图谱(TCGA)和癌症细胞系百科全书(CCLE)数据库检查 BC 中 ASF1B 的存在。此外,进行了相关性分析,以评估 BC 通路评分与 ASF1B 之间的关联。使用 Western blot 和 RT-PCR 检测 BC 细胞中 ASF1B 的表达。在活体内和活体外进行了多项研究,以确认 ASF1B 参与调节 BC 细胞中的生物学过程。

结果

我们对数据库的检查表明,ASF1B 在 BC 细胞中表现出显著的表达水平,并且可能与 BC 细胞的生长和 DNA 修复密切相关。Western blot 和 RT-PCR 的结果表明,BC 细胞中 ASF1B 的表达明显升高。细胞板克隆试验、edu 分析、流式细胞术和 Transwell 实验的结果表明,抑制 ASF1B 极大地阻碍了 BC 细胞的增殖和迁移。在实验室中建立耐药性 BC 细胞系后,抑制 ASF1B 基因表达导致 BC 细胞对顺铂的耐药性显著降低。通过流式细胞术和 Western blot 检测得到证实。我们的体内研究结果表明,抑制 ASF1B 导致病理状况改善、对顺铂的耐药性降低以及 BC 在小鼠中的生长受到抑制。

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