<p>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.</p> Graphical abstract <p></p>

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

  • Aikang Zhang,
  • Yongbin Zheng

摘要

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.

Graphical abstract