Abstract
Colorectal cancer (CRC) is the third most prevalent world cancer and oncogenic β-catenin is frequently dysregulated in CRC. Long noncoding RNAs (lncRNAs) play critical roles in colorectal tumorigenesis; however, the contributions of lncRNAs to human CRC remain largely unknown. In this study, we report that LINC00265 is upregulated and predicts poor clinical outcome in human patients with CRC. Depletion of LINC00265 and ZMIZ2 distinctly attenuates colorectal tumorigenesis in mice. Mechanistically, LINC00265 augments ZMIZ2 expression by acting as an endogenous sponge against several miRNAs, which directly target ZMIZ2 expression. Moreover, ZMIZ2 recruits the enzyme USP7, which deubiquitylates and stabilizes β-catenin, thereby facilitating colorectal tumorigenesis. In addition, β-catenin mediates LINC00265 and ZMIZ2 oncogenic phenotypes. Taken together, the LINC00265-ZMIZ2-β-catenin signaling axis plays a critical role in the colorectal tumorigenesis, which may be a potential therapeutic target.
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Acknowledgements
We thank Professors Hongbing Shu (Wuhan University, Wuhan, China) and Jinxiang Zhang (Wuhan Union Hospital, Wuhan) for providing plasmids and CRC patient samples, respectively. This work was supported by grants from the National Key R&D Program of China (2016YFC1302300) and National Nature Science Foundation of China (81772609, 81802782).
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Zhu, Y., Gu, L., Lin, X. et al. LINC00265 promotes colorectal tumorigenesis via ZMIZ2 and USP7-mediated stabilization of β-catenin. Cell Death Differ 27, 1316–1327 (2020). https://doi.org/10.1038/s41418-019-0417-3
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DOI: https://doi.org/10.1038/s41418-019-0417-3
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