Zhang Chao, Wu Shuai
Department of Strabismus and Pediatric Ophthalmology, the Second Hospital of Jilin University, 130041, Changchun, P. R. China.
Department of Orbital Disease and Ocular Plastic Surgery, the Second Hospital of Jilin University, 130041, Changchun, P. R. China.
Cell Death Discov. 2023 Apr 19;9(1):132. doi: 10.1038/s41420-023-01429-7.
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.
近年来，人们对异常染色质调控过程在致癌作用中的治疗价值的研究兴趣日益浓厚。我们开展这项研究旨在探索染色质调节因子RuvB样蛋白1（RUVBL1）在葡萄膜黑色素瘤（UVM）中的可能致癌机制。在生物信息学数据中检索RUVBL1的表达模式。在公开可用数据库中分析RUVBL1表达与UVM患者预后之间的相关性。预测RUVBL1的下游靶基因，并通过免疫共沉淀进一步验证。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，并且RUVBL1是UVM患者的独立预后因素。引入经RUVBL1敲低处理的UVM细胞进行体外研究。采用CCK-8法、流式细胞术、划痕试验、Transwell试验和蛋白质免疫印迹分析来检测所得UVM细胞的增殖、凋亡、迁移、侵袭及细胞周期分布。体外细胞实验数据表明，UVM细胞中RUVBL1表达显著增加，RUVBL1敲低抑制了UVM细胞的增殖、侵袭和迁移，同时凋亡率增加且细胞周期进程受阻。综上所述，RUVBL1通过增加染色质重塑及随后的CTNNB1转录活性来增强UVM细胞的恶性生物学特性。
