Circ-CCT2 (hsa_circ_0000418) 是一种源自 CCT2 基因的新型环状 RNA。然而，circ-CCT2的表达及其在肝母细胞瘤中的作用尚不清楚。本研究旨在研究circ-CCT2在肝母细胞瘤发生发展中的作用。收集肝母细胞瘤标本并检测circ-CCT2、TAF15和PTBP1的表达。 CCK-8 和集落形成测定用于细胞增殖分析。通过伤口愈合和跨孔实验评估迁移和侵袭能力。通过 FISH、RNA pull-down 和 RIP 验证了 circ-CCT2、TAF15 和 PTBP1 之间的相互作用。 SKL2001 用作 Wnt/β-连环蛋白途径的激动剂。建立小鼠皮下肝母细胞瘤模型，研究circ-CCT2在体内肝母细胞瘤中的功能。Circ-CCT2在肝母细胞瘤中显着上调。 circ-CCT2 的过度表达激活 Wnt/β-catenin 信号传导并促进肝母细胞瘤进展，而 circ-CCT2 的敲低则产生相反的效果。此外，TAF15和PTBP1在肝母细胞瘤组织和细胞中均上调。肝母细胞瘤中TAF15与circ-CCT2、PTBP1的表达呈正相关。此外，circ-CCT2 招募并上调 TAF15 蛋白以稳定 PTBP1 mRNA 并触发肝母细胞瘤中的 Wnt/β-catenin 信号传导。 TAF15 或 PTBP1 的过表达可逆转 circ-CCT2 介导的肝母细胞瘤进展抑制的敲低。 SKL2001介导的Wnt/β-catenin信号激活逆转了circ-CCT2、TAF15或PTBP1沉默的抗肿瘤作用。Circ-CCT2稳定PTBP1 mRNA并通过募集和上调TAF15蛋白来激活Wnt/β-catenin信号，从而促进肝母细胞瘤进展。我们的研究结果加深了对肝母细胞瘤发病机制的理解，并提出了潜在的治疗靶点。版权所有 © 2023 作者。由爱思唯尔公司出版。保留所有权利。

Circ-CCT2 (hsa_circ_0000418) is a novel circular RNA that stems from the CCT2 gene. However, the expression of circ-CCT2 and its roles in hepatoblastoma are unknown. Our study aims to study the circ-CCT2 roles in hepatoblastoma development.Hepatoblastoma specimens were collected for examining the expression of circ-CCT2, TAF15 and PTBP1. CCK-8 and colony formation assays were applied for cell proliferation analysis. Migratory and invasive capacities were evaluated through wound healing and transwell assays. The interaction between circ-CCT2, TAF15 and PTBP1 was validated by FISH, RNA pull-down and RIP. SKL2001 was used as an agonist of the Wnt/β-catenin pathway. A subcutaneous mouse model of hepatoblastoma was established for examining the function of circ-CCT2 in hepatoblastoma in vivo.Circ-CCT2 was significantly upregulated in hepatoblastoma. Overexpression of circ-CCT2 activated Wnt/β-catenin signaling and promoted hepatoblastoma progression, whereas knockdown of circ-CCT2 exerted opposite effects. Moreover, both TAF15 and PTBP1 were upregulated in hepatoblastoma tissues and cells. TAF15 was positively correlated with the expression of circ-CCT2 and PTBP1 in hepatoblastoma. Furthermore, circ-CCT2 recruited and upregulated TAF15 protein to stabilize PTBP1 mRNA and trigger Wnt/β-catenin signaling in hepatoblastoma. Overexpression of TAF15 or PTBP1 reversed knockdown of circ-CCT2-mediated suppression of hepatoblastoma progression. SKL2001-mediated activation of Wnt/β-catenin signaling reversed the anti-tumor effects of silencing of circ-CCT2, TAF15 or PTBP1.Circ-CCT2 stabilizes PTBP1 mRNA and activates Wnt/β-catenin signaling through recruiting and upregulating TAF15 protein, thus promoting hepatoblastoma progression. Our findings deepen the understanding of hepatoblastoma pathogenesis and suggest potential therapeutic targets.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.