视网膜母细胞瘤（RB）是最常见的眼内癌症之一，五岁以下婴幼儿的患病率最高。文献中的大量研究结果说明了环状 RNA (circRNA) 在人类恶性肿瘤（包括 RB）中的参与和重要性。目前的研究试图破译新型circRNA hsa_circ_0078136在RB进展中的确切作用和潜在机制。通过qRT-PCR评估了RB肿瘤和细胞系中的hsa_circ_0078136表达。通过进行 CCK8 测定、transwell 测定、凋亡和 IL-17 信号配体分子的蛋白质印迹以及皮下异种移植肿瘤模型来检查 hsa_circ_0078136 在 RB 中的重要性。此外，通过生物信息学、蛋白质印迹和RIP测定确定了circRNA与真核翻译起始因子4A3（EIF4A3）的相互作用。RB肿瘤样本和细胞中hsa_circ_0078136表达降低。此外，其过度表达限制了 RB 细胞的体外致癌特性。此外，hsa_circ_0078136过表达降低了RB细胞系中IL-17信号通路的细胞因子配体分子的蛋白水平。在体内，hsa_circ_0078136 在皮下肿瘤异种移植物中过度表达可减少肿瘤生长。我们还观察到EIF4A3与SHRPH前体mRNA转录本中hsa_circ_0078136的下游侧翼序列结合，并且EIF4A3过表达降低了hsa_circ_0078136的表达，表明EIF4A3抑制了hsa_circ_0078136的形成。我们的结果表明hsa_circ_0078136受EIF4A3调节并发挥肿瘤抑制因子的作用通过 RB 中的 IL-17 信号通路。© 2024。作者获得 Springer Nature B.V. 的独家许可。

Retinoblastoma (RB) is one of the most common intraocular cancers, with the highest prevalence among infants and young children under the age five. Numerous findings across the literature illustrate the involvement and significance of circular RNAs (circRNAs) in human malignancies, including RB. The current investigation attempted to decipher the exact roles and underlying mechanisms of a novel circRNA, hsa_circ_0078136, in RB progression.The hsa_circ_0078136 expression was evaluated in RB tumors and cell lines via qRT-PCR. The significance of hsa_circ_0078136 in RB was examined by performing CCK8 assay, transwell assays, western blotting of apoptotic and IL-17 signaling ligand molecules, and a subcutaneous xenograft tumor model. In addition, the interaction of circRNA and eukaryotic translation initiation factor 4A3 (EIF4A3) was determined with bioinformatics, western blot, and RIP assay.The hsa_circ_0078136 expression was reduced in RB tumor samples and cells. Additionally, its overexpression restricted the oncogenic properties of RB cells in vitro. Moreover, hsa_circ_0078136 overexpression lowered the protein levels of cytokine ligand molecules of IL-17 signaling pathway in RB cell lines. In vivo, hsa_circ_0078136 overexpression in subcutaneous tumor xenografts reduced tumor growth. We also observed that EIF4A3 binds to the downstream flanking sequence of hsa_circ_0078136 in the SHRPH pre-mRNA transcript, and EIF4A3 overexpression reduced hsa_circ_0078136 expression, suggesting that EIF4A3 inhibited hsa_circ_0078136 formation.Our results demonstrate that hsa_circ_0078136 is regulated by EIF4A3 and functions as a tumor suppressor via the IL-17 signaling pathway in RB.© 2024. The Author(s), under exclusive licence to Springer Nature B.V.