结直肠癌（CRC）是全球第二大常见恶性肿瘤，其发病率逐年上升。早期诊断和治疗对于改善结直肠癌患者的预后至关重要。环状RNA是具有闭环结构的非编码RNA，在肿瘤发展中发挥重要作用。然而，人们对环状RNA在CRC中的作用知之甚少。利用生物信息学分析在CRC circRNA微阵列中筛选环状RNA hsa_circ_0000467，并通过原位杂交测定hsa_circ_0000467在CRC组织中的表达。评估 hsa_circ_0000467 的表达水平与 CRC 患者临床特征之间的关联。然后，通过体外 CCK8 测定、EdU 测定、平板集落形成测定、伤口愈合测定和 Transwell 测定以及体内 CRC 小鼠模型评估 hsa_circ_0000467 在 CRC 生长和转移中的作用。进行蛋白质组分析和蛋白质印迹来研究 hsa_circ_0000467 对 c-Myc 信号传导的影响。进行多核糖体分析、RT-qPCR 和双荧光素酶报告基因测定，以确定 hsa_circ_0000467 对 c-Myc 翻译的影响。通过RNA Pull-down、RNA免疫沉淀（RIP）和免疫荧光染色来评估hsa_circ_0000467对eIF4A3分布的影响。在这项研究中，我们发现环状RNA hsa_circ_0000467在结直肠癌中高表达，并且与结直肠癌的不良预后显着相关。结直肠癌患者。体外和体内实验表明hsa_circ_0000467促进结直肠癌细胞的生长和转移。从机制上讲，hsa_circ_0000467 结合 eIF4A3 以抑制其核转位。此外，它还可以作为支架分子，在细胞质中结合eIF4A3和c-Myc mRNA形成复合物，从而促进c-Myc的翻译。反过来，c-Myc 上调其下游靶标，包括细胞周期相关因子 cyclin D2 和 CDK4 以及紧密连接相关因子 ZEB1，并下调 E-cadherin，最终促进 CRC 的生长和转移。我们的研究结果显示hsa_circRNA_0000467 通过促进 eIF4A3 介导的 c-Myc 翻译在 CRC 进展中发挥作用。该研究为CRC的诊断和治疗提供了理论基础和分子靶点。© 2024。作者。

Colorectal cancer (CRC) is the second most common malignant tumor worldwide, and its incidence rate increases annually. Early diagnosis and treatment are crucial for improving the prognosis of patients with colorectal cancer. Circular RNAs are noncoding RNAs with a closed-loop structure that play a significant role in tumor development. However, the role of circular RNAs in CRC is poorly understood.The circular RNA hsa_circ_0000467 was screened in CRC circRNA microarrays using a bioinformatics analysis, and the expression of hsa_circ_0000467 in CRC tissues was determined by in situ hybridization. The associations between the expression level of hsa_circ_0000467 and the clinical characteristics of CRC patients were evaluated. Then, the role of hsa_circ_0000467 in CRC growth and metastasis was assessed by CCK8 assay, EdU assay, plate colony formation assay, wound healing assay, and Transwell assay in vitro and in a mouse model of CRC in vivo. Proteomic analysis and western blotting were performed to investigate the effect of hsa_circ_0000467 on c-Myc signaling. Polysome profiling, RT‒qPCR and dual-luciferase reporter assays were performed to determine the effect of hsa_circ_0000467 on c-Myc translation. RNA pull-down, RNA immunoprecipitation (RIP) and immunofluorescence staining were performed to assess the effect of hsa_circ_0000467 on eIF4A3 distribution.In this study, we found that the circular RNA hsa_circ_0000467 is highly expressed in colorectal cancer and is significantly correlated with poor prognosis in CRC patients. In vitro and in vivo experiments revealed that hsa_circ_0000467 promotes the growth and metastasis of colorectal cancer cells. Mechanistically, hsa_circ_0000467 binds eIF4A3 to suppress its nuclear translocation. In addition, it can also act as a scaffold molecule that binds eIF4A3 and c-Myc mRNA to form complexes in the cytoplasm, thereby promoting the translation of c-Myc. In turn, c-Myc upregulates its downstream targets, including the cell cycle-related factors cyclin D2 and CDK4 and the tight junction-related factor ZEB1, and downregulates E-cadherin, which ultimately promotes the growth and metastasis of CRC.Our findings revealed that hsa_circRNA_0000467 plays a role in the progression of CRC by promoting eIF4A3-mediated c-Myc translation. This study provides a theoretical basis and molecular target for the diagnosis and treatment of CRC.© 2024. The Author(s).