Abstract
The abnormal activation of the nuclear factor-kappa B (NF-κB) signaling pathway is an important precipitating factor for the inception and development of colorectal cancer (CRC), one of the most common tumors worldwide. As a pro-apoptotic transcription factor, monocyte chemotactic protein-induced protein 1 (MCPIP1) has been closely associated with many tumor types. In the present study, the expression of MCPIP1 was firstly discovered reduced in CRC tissues and correlated with poor patient prognosis. The decreased expression was caused by promoter hypermethylation. Overexpressed MCPIP1 was found to inhibit the proliferative and migratory abilities of CRC cells, whereas knockdown of MCPIP1 produced the opposite result. The subsequent investigation demonstrated that MCPIP1 exerted its “anti-cancer” effect by suppression of the NF-κB signaling pathway through negative regulation of K63-linked ubiquitylation of TNF receptor associated factor 6 (TRAF6). Therefore, our results indicate a prognostic marker for CRC and a theoretical basis for MCPIP1 as a treatment.
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Data availability
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Funding
This work is supported by the grants from the National Natural Science Foundation of China (No. 81702312) and the Natural Science Foundation of Guangdong Province (No. 2017A030310489).
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WY, WH, and YL contributed to the conceptualization and design of the experiment. WY, JR, ZZ, and AL contributed to the methodology, investigation, and data curation. YC and YL contributed to the software, validation, and visualization. WY also contributed to the supervision and funding acquisition. All authors contributed to the data analysis, paper writing, and approved submission.
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Ye, W., Cui, Y., Rong, J. et al. MCPIP1 Suppresses the NF-κB Signaling Pathway Through Negative Regulation of K63-Linked Ubiquitylation of TRAF6 in Colorectal Cancer. Cancer Gene Ther 30, 96–107 (2023). https://doi.org/10.1038/s41417-022-00528-4
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DOI: https://doi.org/10.1038/s41417-022-00528-4
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