Curcumin Inhibits Retinoblastoma Cell Proliferation by miR-26a Targeting the Tumor Suppressor Gene Rb1 in Y79 Cells

J. Bai
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引用次数: 2

Abstract

The retinoblastoma (Rb1) gene is one of the most important tumor suppressor genes. Dysfunction of Rb protein drives tumorigenesis by overcoming barriers to cellular proliferation. Consequently, factors modulating Rb function are of great clinical import. Here, we show that miR-26a was differentially expressed in human retinoblastoma cells, tissues and serums from retinoblastoma patients, compared with human retinal microvascular endothelial cells, non-tumor tissues and serums from healthy children, and that it tightly regulated the expression of Rb1 by specifically targeting a conserved sequence motif in its 3′ UTR, leading to low expression of Rb1. In vitro experiments determined that miR-26a directly participated in the regulation of cell proliferation of human Y79 RB cells. Our results also suggest that curcumin modulated the miR-26a expression profile, thereby exerting its anti-proliferation effects on Y79 RB cells via up-regulation of Rb1. To our knowledge, these data indicate for the first time that miR-26a directly regulates cell proliferation by targeting Rb1 in retinoblastoma and that miR-26a could be a potential therapeutic approach for retinoblastoma.
姜黄素通过miR-26a靶向肿瘤抑制基因Rb1抑制Y79细胞中的视网膜母细胞瘤细胞增殖
视网膜母细胞瘤(Rb1)基因是最重要的肿瘤抑制基因之一。Rb蛋白功能障碍通过克服细胞增殖障碍驱动肿瘤发生。因此,调节Rb功能的因子具有重要的临床意义。在这里,我们发现miR-26a在人视网膜母细胞瘤细胞、视网膜母细胞瘤患者的组织和血清中与人视网膜微血管内皮细胞、非肿瘤组织和健康儿童的血清中表达差异,并且miR-26a通过特异性靶向其3 ' UTR中的保守序列基序严格调节Rb1的表达,导致Rb1的低表达。体外实验确定miR-26a直接参与人Y79 RB细胞增殖的调控。我们的研究结果还表明,姜黄素调节了miR-26a的表达谱,从而通过上调Rb1对Y79 RB细胞发挥其抗增殖作用。据我们所知,这些数据首次表明miR-26a在视网膜母细胞瘤中通过靶向Rb1直接调节细胞增殖,miR-26a可能是视网膜母细胞瘤的一种潜在治疗方法。
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