近年来,人们对异常染色质调节过程在致癌过程中的治疗价值的研究越来越感兴趣。我们的研究旨在探索染色质调节剂 RuvB 样蛋白 1 (RUVBL1) 在葡萄膜黑色素瘤 (UVM) 中可能的致癌机制。在生物信息学数据中检索了 RUVBL1 的表达模式。在公开可用的数据库中分析 RUVBL1 表达与 UVM 患者预后之间的相关性。通过共免疫沉淀预测并进一步验证了 RUVBL1 的下游靶基因。生物信息学分析结果表明,RUVBL1可能通过调节染色质重塑与CTNNB1的转录活性相关,RUVBL1可作为UVM患者的独立预后因素。引入了用 RUVBL1 敲低操作的 UVM 细胞用于体外研究。采用CCK-8法、流式细胞术、划痕法、Transwell法和Western blot法检测UVM细胞增殖、凋亡、迁移、侵袭和细胞周期分布。体外细胞实验数据显示,UVM 细胞中 RUVBL1 表达显着增加,RUVBL1 敲低抑制了 UVM 细胞的增殖、侵袭和迁移,伴随着细胞凋亡率增加和细胞周期进程受阻。综上所述,RUVBL1通过增加CTNNB1的染色质重塑和随后的转录活性来增强UVM细胞的恶性生物学特性。Transwell实验和Western blot分析用于检测所得UVM细胞增殖、凋亡、迁移、侵袭和细胞周期分布。体外细胞实验数据显示,UVM 细胞中 RUVBL1 表达显着增加,RUVBL1 敲低抑制了 UVM 细胞的增殖、侵袭和迁移,伴随着细胞凋亡率增加和细胞周期进程受阻。综上所述,RUVBL1通过增加CTNNB1的染色质重塑和随后的转录活性来增强UVM细胞的恶性生物学特性。Transwell实验和Western blot分析用于检测所得UVM细胞增殖、凋亡、迁移、侵袭和细胞周期分布。体外细胞实验数据显示,UVM 细胞中 RUVBL1 表达显着增加,RUVBL1 敲低抑制了 UVM 细胞的增殖、侵袭和迁移,伴随着细胞凋亡率增加和细胞周期进程受阻。综上所述,RUVBL1通过增加CTNNB1的染色质重塑和随后的转录活性来增强UVM细胞的恶性生物学特性。体外细胞实验数据显示,UVM 细胞中 RUVBL1 表达显着增加,RUVBL1 敲低抑制了 UVM 细胞的增殖、侵袭和迁移,伴随着细胞凋亡率增加和细胞周期进程受阻。综上所述,RUVBL1通过增加CTNNB1的染色质重塑和随后的转录活性来增强UVM细胞的恶性生物学特性。体外细胞实验数据显示,UVM 细胞中 RUVBL1 表达显着增加,RUVBL1 敲低抑制了 UVM 细胞的增殖、侵袭和迁移,伴随着细胞凋亡率增加和细胞周期进程受阻。综上所述,RUVBL1通过增加CTNNB1的染色质重塑和随后的转录活性来增强UVM细胞的恶性生物学特性。
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RUVBL1-modulated chromatin remodeling alters the transcriptional activity of oncogenic CTNNB1 in uveal melanoma
Recent years have witnessed an increasing research interest in the therapeutic value of aberrant chromatin regulatory processes in carcinogenesis. Our study was performed to explore the possible carcinogenic mechanism of the chromatin regulator RuvB-like protein 1 (RUVBL1) in uveal melanoma (UVM). The expression pattern of RUVBL1 was retrieved in bioinformatics data. The correlation between RUVBL1 expression and the prognosis of patients with UVM was analyzed in publicly available database. The downstream target genes of RUVBL1 were predicted and further verified by co-immunoprecipitation. The bioinformatics analysis results showed that RUVBL1 may be associated with the transcriptional activity of CTNNB1 by regulating chromatin remodeling, and that RUVBL1 functioned as an independent prognostic factor for patients with UVM. The UVM cells manipulated with RUVBL1 knockdown were introduced for in vitro investigation. CCK-8 assay, flow cytometry, scratch assay, Transwell assay and Western blot analysis were used for detection on the resultant UVM cell proliferation, apoptosis, migration, invasion and cell cycle distribution. In vitro cell experimental data showed that RUVBL1 expression was significantly increased in UVM cells and RUVBL1 knockdown inhibited the proliferation, invasion and migration of UVM cells, accompanied by augmented apoptosis rate and blocked cell cycle progression. To sum up, RUVBL1 enhances the malignant biological characteristics of UVM cells by increasing the chromatin remodeling and subsequent transcription activity of CTNNB1.