研究动态
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通过组蛋白修饰促进SOX2基因的过度表达:SOX2通过抑制细胞凋亡和促进细胞增殖,增强人类前列腺和乳腺癌的进展。

Overexpression of SOX2 Gene by Histone Modifications: SOX2 Enhances Human Prostate and Breast Cancer Progression by Prevention of Apoptosis and Enhancing Cell Proliferation.

发表日期:2023 Aug 04
作者: Swayamsiddha Kar, Niharika, Ankan Roy, Samir Kumar Patra
来源: Epigenetics & Chromatin

摘要:

SOX2在肿瘤发展、癌干细胞维持和癌症进展中起着至关重要的作用。目前尚未确定SOX2基因在人类乳腺癌和前列腺癌中的调控机制。我们通过定量逆转录聚合酶链反应(qRT-PCR)、蛋白质免疫印迹和免疫组化来确定前列腺癌和乳腺癌组织及细胞系中的SOX2表达,并通过基因敲除以及表观遗传调节剂和染色质免疫沉淀探究其促肿瘤特性,如细胞增殖、迁移和凋亡。前列腺癌和乳腺癌组织表现出极高的SOX2表达。所有癌细胞系DU145和PC3(前列腺)和MCF7和MDA-MB-231(乳腺)均显示出SOX2的高表达。抑制SOX2大大降低了细胞增殖和迁移。表观遗传调节剂提高了这两种癌症类型中SOX2基因的表达水平。SOX2启动子的DNA甲基化模式并不能明显解释SOX2的过表达。SOX2基因启动子的激活是由于H3K4me3和H3K9acS10p的高度沉积以及H3K9me3和H3K27me3的明显降低。组蛋白修饰在肿瘤发展和癌症进展中过表达SOX2中起着至关重要的作用。这些发现表明,联合靶向SOX2及其活性表观遗传修饰酶可能是有效治疗侵袭性前列腺癌和乳腺癌的途径。© 2023 S. Karger AG, Basel.
SOX2 plays a crucial role in tumor development, cancer stem cell maintenance, and cancer progression. Mechanisms of SOX2 gene regulation in human breast and prostate cancers are not established yet.SOX2 expression in prostate and breast cancer tissues and cell lines was determined by qRT-PCR, Western blot, and immunochemistry, followed by the investigation of pro-tumorigenic properties like cell proliferation, migration, and apoptosis by gene knockdown and treatment with epigenetic modulators and ChIP.Prostate and breast cancer tissues showed very high expression of SOX2. All cancer cell lines DU145 and PC3 (prostate) and MCF7 and MDA-MB-231 (breast) exhibited high expression of SOX2. Inhibition of SOX2 drastically decreased cell proliferation and migration. Epigenetic modulators enhanced SOX2 gene expression in both cancer types. DNA methylation pattern in SOX2 promoter could not be appreciably counted for SOX2 overexpression. Activation of SOX2 gene promoter was due to very high deposition of H3K4me3 and H3K9acS10p and drastic decrease of H3K9me3 and H3K27me3.Histone modification is crucial for the overexpression of SOX2 during tumor development and cancer progression. These findings show the avenue of co-targeting SOX2 and its active epigenetic modifier enzymes to effectively treat aggressive prostate and breast cancers.© 2023 S. Karger AG, Basel.