研究动态
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结肠癌中组蛋白乙酰转移酶 TIP60 对 HDAC3 转录的负调控。

Negative regulation of HDAC3 transcription by histone acetyltransferase TIP60 in colon cancer.

发表日期:2024 May 28
作者: Seong Yun Lee, Junyoung Park, Sang Beom Seo
来源: Cellular & Molecular Immunology

摘要:

结肠癌是全球第三大常见癌症。在结肠癌中,组蛋白脱乙酰酶 3 (HDAC3) 的表达上调,而 tat 相互作用蛋白 60 kDa (TIP60) 的表达下调。然而,HDAC3和TIP60在结肠癌中的关系尚未明确阐明。我们研究了TIP60是否可以调节HDAC3的表达并抑制结肠癌细胞的增殖。RNA测序数据(GSE108834)显示HDAC3的表达受TIP60的调节。随后,我们生成了 TIP60 敲低的 HCT116 细胞,并通过蛋白质印迹和逆转录定量聚合酶链反应 (RT-qPCR) 检查了 HDAC3 的表达。我们使用公开数据集检查了 HDAC3 在各种癌症中的表达模式。使用双荧光素酶测定验证 HDAC3 的启动子活性,并使用 GeneCards 和 Promo 数据库鉴定与 HDAC3 结合的转录因子,然后使用染色质免疫沉淀-定量聚合酶链反应进行验证。使用 HCT116 细胞系的集落形成测定和荧光激活细胞分选分析来评估细胞增殖和凋亡。响应 TIP60 敲低,HDAC3 的表达水平和启动子活性增加。相反,当TIP60过表达下调HDAC3时,HCT116细胞增殖受到抑制,促进细胞凋亡。TIP60在HDAC3转录调控中发挥着至关重要的作用,从而影响结肠癌细胞的增殖和凋亡。因此,TIP60 可能通过抑制结肠癌细胞中的 HDAC3 表达而发挥肿瘤抑制剂的作用。© 2024。作者。
Colon cancer is the third most common cancer globally. The expression of histone deacetylase 3 (HDAC3) is upregulated, whereas the expression of tat interactive protein, 60 kDa (TIP60) is downregulated in colon cancer. However, the relationship between HDAC3 and TIP60 in colon cancer has not been clearly elucidated.We investigated whether TIP60 could regulate the expression of HDAC3 and suppress colon cancer cell proliferation.RNA sequencing data (GSE108834) showed that HDAC3 expression was regulated by TIP60. Subsequently, we generated TIP60-knockdown HCT116 cells and examined the expression of HDAC3 by western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). We examined the expression pattern of HDAC3 in various cancers using publicly available datasets. The promoter activity of HDAC3 was validated using a dual-luciferase assay, and transcription factors binding to HDAC3 were identified using GeneCards and Promo databases, followed by validation using chromatin immunoprecipitation-quantitative polymerase chain reaction. Cell proliferation and apoptosis were assessed using colony formation assays and fluorescence-activated cell sorting analysis of HCT116 cell lines.In response to TIP60 knockdown, the expression level and promoter activity of HDAC3 increased. Conversely, when HDAC3 was downregulated by overexpression of TIP60, proliferation of HCT116 cells was inhibited and apoptosis was promoted.TIP60 plays a crucial role in the regulation of HDAC3 transcription, thereby influencing cell proliferation and apoptosis in colon cancer. Consequently, TIP60 may function as a tumor suppressor by inhibiting HDAC3 expression in colon cancer cells.© 2024. The Author(s).