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环状RNA_0000847通过与胰岛素样生长因子2结合蛋白2(IGF2BP2)结合以增强IGF2信使核糖核酸(mRNA)稳定性,从而促进结直肠癌的迁移、侵袭及上皮-间质转化过程。

Circ_0000847 promotes the migration, invasion, and EMT process in colorectal cancer through binding to IGF2BP2 to enhance IGF2 mRNA stability.

作者信息

Zhang Aikang, Zheng Yongbin

机构信息

Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, No. 99, Zhangzhidong Road, Wuchang District, Wuhan, 430000, Hubei, China.

出版信息

Med Oncol. 2025 Aug 22;42(10):436. doi: 10.1007/s12032-025-02877-0.

DOI:10.1007/s12032-025-02877-0
PMID:40844647
Abstract

Colorectal cancer (CRC) stands as one of the most prevalent forms of malignant gastrointestinal tumors. Circular RNAs (circRNAs) could serve as promising targets for therapeutic intervention in CRC. This study aims to uncover the significance and influence of circRNAs within the landscape of CRC. CircRNA microarray, RNase R assay, and fluorescence in situ hybridization were conducted to verify the expression and characteristics of circRNA. The biological behaviors of CRC cells were evaluated by cell counting kit-8, transwell assay, and wound-healing assay. The underlying mechanism was revealed using quantitative real-time PCR, Western bot, silver staining assay, biotin-labeled RNA pulldown, and RNA immunoprecipitation. The results indicated that circ_0000847, a CRC-associated circRNA, was over-expressed in CRC. Inhibition of circ_0000847 effectively restrained the migratory and invasive behaviors of CRC cells, alongside suppressing their epithelial-mesenchymal transition (EMT). Circ_0000847 bound to IGF2BP2, thereby enhancing the IGF2 mRNA stability. Importantly, overexpression of IGF2 abrogated the inhibitory effect of circ_0000847 depletion on CRC cellular processes. In addition, circ_0000847 promoted tumor growth in vivo. In summary, by engaging with IGF2BP2, circ_0000847 plays a role in stabilizing IGF2 mRNA, which in turn curtails the advancement of CRC. Hence, circ_0000847 could serve as an innovative and potentially pivotal target for the development of CRC therapies.

摘要

结直肠癌(CRC)是最常见的恶性胃肠道肿瘤之一。环状RNA(circRNAs)有望成为CRC治疗干预的靶点。本研究旨在揭示circRNAs在CRC中的意义和影响。进行环状RNA微阵列、核糖核酸酶R分析和荧光原位杂交以验证环状RNA的表达和特征。通过细胞计数试剂盒-8、Transwell分析和伤口愈合分析评估CRC细胞的生物学行为。使用定量实时PCR、蛋白质免疫印迹、银染分析、生物素标记的RNA下拉和RNA免疫沉淀揭示潜在机制。结果表明,circ_0000847是一种与CRC相关的环状RNA,在CRC中过表达。抑制circ_0000847可有效抑制CRC细胞的迁移和侵袭行为,并抑制其上皮-间质转化(EMT)。circ_0000847与IGF2BP2结合,从而提高IGF2 mRNA的稳定性。重要的是,IGF2的过表达消除了circ_0000847缺失对CRC细胞过程的抑制作用。此外,circ_0000847在体内促进肿瘤生长。总之,通过与IGF2BP2结合,circ_0000847在稳定IGF2 mRNA中发挥作用,进而抑制CRC的进展。因此,circ_0000847可作为CRC治疗开发的一个创新且可能关键的靶点。

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本文引用的文献

1
CircRNA: An emerging star in plant research: A review.环状 RNA:植物研究中的新兴明星:综述。
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Hsa_circRNA_001676 accelerates the proliferation, migration and stemness in colorectal cancer through regulating miR-556-3p/G3BP2 axis.Hsa_circRNA_001676 通过调控 miR-556-3p/G3BP2 轴促进结直肠癌细胞的增殖、迁移和干性。
Sci Rep. 2023 Oct 26;13(1):18353. doi: 10.1038/s41598-023-45164-6.
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Intergenic CircRNA Inhibits Colorectal Cancer Progression by Modulating Biogenesis in a KSRP-Dependent Manner.基因间环状 RNA 通过依赖于 KSRP 的方式调控生物发生抑制结直肠癌进展。
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m6A-modified circABCC4 promotes stemness and metastasis of prostate cancer by recruiting IGF2BP2 to increase stability of CCAR1.m6A 修饰的 circABCC4 通过招募 IGF2BP2 增加 CCAR1 的稳定性来促进前列腺癌的干性和转移。
Cancer Gene Ther. 2023 Oct;30(10):1426-1440. doi: 10.1038/s41417-023-00650-x. Epub 2023 Aug 10.
7
Mechanism of epithelial-mesenchymal transition in cancer and its regulation by natural compounds.癌症中上皮-间充质转化的机制及其受天然化合物的调控。
Med Res Rev. 2023 Jul;43(4):1141-1200. doi: 10.1002/med.21948. Epub 2023 Mar 17.
8
Circular RNA circ-TNPO3 inhibits clear cell renal cell carcinoma metastasis by binding to IGF2BP2 and destabilizing SERPINH1 mRNA.环状 RNA circ-TNPO3 通过与 IGF2BP2 结合并使 SERPINH1 mRNA 不稳定来抑制透明细胞肾细胞癌转移。
Clin Transl Med. 2022 Jul;12(7):e994. doi: 10.1002/ctm2.994.
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CircEZH2/miR-133b/IGF2BP2 aggravates colorectal cancer progression via enhancing the stability of mA-modified CREB1 mRNA.环状 EZH2/miR-133b/IGF2BP2 通过增强 mA 修饰的 CREB1 mRNA 的稳定性促进结直肠癌的进展。
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Specific expression and functions of circular RNAs.环状RNA的特异性表达及功能
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