最近的研究强调了环状 RNA (circRNA) 在包括神经母细胞瘤 (NB) 在内的各种癌症中的重要性。具体而言，circ-SHPRH（一种独特的 circRNA）已被发现可以通过隔离 miRNA 或产生 SHPRH-146aa 蛋白来抑制肿瘤生长。为了探讨 circ-SHPRH 在 NB 中的参与及其在基因治疗中的潜在应用，本研究使用实时 PCR 和检测方法检测了 94 个 NB 组织和细胞系（SK-N-BE(2)、SH-SY5Y）中的 circ-SHPRH 表达。荧光原位杂交（FISH）。进行了功能测定，包括 NB 细胞系中的过表达和敲低实验以及体内研究。 RNA-seq 分析揭示了 circ-SHPRH 与关键细胞周期调节因子 P21 (CDKN1A) 通路之间的相关性。通过 PCR 和其他技术验证证实 circ-SHPRH 上调 P21 表达。此外，通过 SHPRH-146aa 表达分析证实了 circ-SHPRH 在 P21-CDK 通路中的调节作用。值得注意的是，腺病毒介导的 circ-SHPRH 过表达有效抑制了 NSG 小鼠中的 NB 肿瘤生长，而 circ-SHPRH 与依维莫司联合显示了 NB 治疗的潜力。这项研究阐明了 circ-SHPRH 在 NB 中的显着意义及其在基因治疗中的前景用途，从而为创新治疗方法铺平了道路。版权所有 © 2024。由 Elsevier B.V. 出版。

Recent research has underscored the significance of circular RNAs (circRNAs) in various cancers, including neuroblastoma (NB). Specifically, circ-SHPRH, a unique circRNA, has been revealed to inhibit tumor growth by sequestering miRNAs or producing the SHPRH-146aa protein. To explore circ-SHPRH's involvement in NB and its potential application in gene therapy, this study examined circ-SHPRH expression in 94 NB tissues and cell lines (SK-N-BE(2), SH-SY5Y) using real-time PCR and fluorescence in situ hybridization (FISH). Functional assays encompassing both overexpression and knockdown experiments in NB cell lines, as well as in vivo investigations, were conducted. RNA-seq analysis revealed a correlation between circ-SHPRH and the pathway of P21 (CDKN1A), a pivotal cell cycle regulator. Validation through PCR and other techniques confirmed that circ-SHPRH upregulated P21 expression. Furthermore, the regulatory role of circ-SHPRH in the P21-CDK pathway was corroborated through SHPRH-146aa expression analysis. Notably, adenovirus-mediated circ-SHPRH overexpression effectively curbed NB tumor growth in NSG mice, while combining circ-SHPRH with everolimus exhibited potential for NB treatment. This study elucidates the remarkable significance of circ-SHPRH in NB and its prospective utility in gene therapy, thereby paving the way for innovative therapeutic approaches.Copyright © 2024. Published by Elsevier B.V.