Retinoblastoma is the most common intraocular cancer with metastatic potential affecting infants and children. Although chemotherapy is available for retinoblastoma, side effects and drug resistance are frequent. Rpl41, encoding ribosomal protein L41 (RPL41), has been identified as a tumor suppressor gene, and its targeted degradation of activating transcription factor 4 (ATF4) produces an antitumor effect. The goal of the present study is to provide experimental evidence for the clinical application of a small peptide regimen in combination with chemotherapy for the treatment of retinoblastoma and to investigate the mechanism of their combined cytotoxicity. It was observed that treatment with the RPL41 peptide alone decreased the viability, migration, and invasion of retinoblastoma Y79 and Weri‐Rb1 cells, in addition to promoting cell apoptosis and cell cycle arrest. Furthermore, RPL41 protein levels showed a significantly decreased trend in retinoblastoma specimens, whereas ATF4 protein levels tended to be increased. Mechanistically, ATF4 degradation as a result of RPL41 peptide treatment was observed in retinoblastoma Y79 and Weri‐Rb1 cells. Most important, low‐dose administration of the RPL41 peptide significantly enhanced the antitumor effect of carboplatin, and further analysis confirmed their synergistic effect as anti‐retinoblastoma therapy, indicating that RPL41 sensitized Y79 and Weri‐Rb1 retinoblastoma cells to carboplatin. Thus, our data provide a preclinical rationale for the exploration of the RPL41 peptide as a potential adjuvant to carboplatin treatment in retinoblastoma.

中文翻译：

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RPL41 通过 ATF4 降解使视网膜母细胞瘤细胞对化疗药物敏感。

视网膜母细胞瘤是最常见的眼内癌症，具有影响婴儿和儿童的转移潜能。虽然化疗可用于视网膜母细胞瘤，但副作用和耐药性很常见。Rpl41编码核糖体蛋白 L41 (RPL41) 的基因已被鉴定为抑癌基因，其靶向降解活化转录因子 4 (ATF4) 产生抗肿瘤作用。本研究的目的是为小肽方案联合化疗治疗视网膜母细胞瘤的临床应用提供实验依据，并探讨其联合细胞毒性的机制。据观察，除了促进细胞凋亡和细胞周期停滞之外，单独用 RPL41 肽处理还降低了视网膜母细胞瘤 Y79 和 Weri-Rb1 细胞的活力、迁移和侵袭。此外，RPL41 蛋白水平在视网膜母细胞瘤标本中显示出显着降低的趋势，而 ATF4 蛋白水平则有增加的趋势。从机制上讲，在视网膜母细胞瘤 Y79 和 Weri-Rb1 细胞中观察到 RPL41 肽处理导致 ATF4 降解。最重要的是，RPL41 肽的低剂量给药显着增强了卡铂的抗肿瘤作用，进一步分析证实了它们作为抗视网膜母细胞瘤治疗的协同作用，表明 RPL41 使 Y79 和 Weri-Rb1 视网膜母细胞瘤细胞对卡铂敏感。因此，我们的数据为探索 RPL41 肽作为卡铂治疗视网膜母细胞瘤的潜在佐剂提供了临床前基本原理。表明 RPL41 使 Y79 和 Weri-Rb1 视网膜母细胞瘤细胞对卡铂敏感。因此，我们的数据为探索 RPL41 肽作为卡铂治疗视网膜母细胞瘤的潜在佐剂提供了临床前基本原理。表明 RPL41 使 Y79 和 Weri-Rb1 视网膜母细胞瘤细胞对卡铂敏感。因此，我们的数据为探索 RPL41 肽作为卡铂治疗视网膜母细胞瘤的潜在佐剂提供了临床前基本原理。