Department of Ophthalmology, Wuhan Asia General Hospital, Wuhan, 430000, Hubei, China.
Department of Ophthalmology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, 430074, Hubei, China.
Int Ophthalmol. 2024 Aug 24;44(1):352. doi: 10.1007/s10792-024-03276-6.
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.
视网膜母细胞瘤（RB）是最常见的眼内癌之一，在五岁以下的婴儿和幼儿中发病率最高。大量文献表明，环状 RNA（circRNA）在包括 RB 在内的人类恶性肿瘤中具有重要作用。本研究试图解析新型环状 RNA hsa_circ_0078136 在 RB 进展中的确切作用和潜在机制。
通过 qRT-PCR 检测 RB 肿瘤和细胞系中的 hsa_circ_0078136 表达。通过 CCK8 检测、Transwell 检测、凋亡和 IL-17 信号配体分子的 Western blot 以及皮下异种移植肿瘤模型检测 hsa_circ_0078136 在 RB 中的意义。此外，通过生物信息学、Western blot 和 RIP 检测确定 circRNA 与真核翻译起始因子 4A3（EIF4A3）的相互作用。
hsa_circ_0078136 在 RB 肿瘤样本和细胞中表达降低。此外，其过表达限制了 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 信号通路细胞因子配体分子的蛋白水平。在体内，hsa_circ_0078136 过表达可降低皮下肿瘤异种移植瘤的生长。我们还观察到，EIF4A3 结合到 SHRPH 前体 mRNA 转录物中 hsa_circ_0078136 的下游侧翼序列，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。
我们的研究结果表明，hsa_circ_0078136 受 EIF4A3 调控，并通过 IL-17 信号通路在 RB 中发挥肿瘤抑制作用。
