Circular RNA hsa_circ_0000467 promotes colorectal cancer progression by promoting eIF4A3-mediated c-Myc translation
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Published:2024-07-31
Issue:1
Volume:23
Page:
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ISSN:1476-4598
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Container-title:Molecular Cancer
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language:en
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Short-container-title:Mol Cancer
Author:
Jiang Xianjie,Peng Mingjing,Liu Qiang,Peng Qiu,Oyang Linda,Li Shizhen,Xu Xuemeng,Shen Mengzhou,Wang Jiewen,Li Haofan,Wu Nayiyuan,Tan Shiming,Lin Jinguan,Xia Longzheng,Tang Yanyan,Luo Xia,Liao Qianjin,Zhou Yujuan
Abstract
Abstract
Background
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.
Methods
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.
Results
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.
Conclusions
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.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Hunan Province
Science and technology innovation Program of Hunan Province
Research Project of Health Commission of Hunan Province
Hunan Provincial Science and Technology Department
Changsha Science and Technology Board
Ascend Foundation of National cancer center
Hunan Cancer Hospital Climb Plan
China Postdoctoral Science Foundation
Publisher
Springer Science and Business Media LLC
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