UTP18-mediated p21 mRNA instability drives adenoma-carcinoma progression in colorectal cancer

Colorectal cancer (CRC) often develops slowly from adenoma, but the underlying mechanism remains un-clear, hampering the prevention or treatment of colorectal adenoma-carcinoma progression. In this study, we use in-depth quantitative proteomics combined with survival analysis, revealing that the ribosome protein U3 small nucleolar RNA-associated protein 18 homolog (UTP18) is consistently upregulated in the progres-sion of colorectal adenoma to carcinoma and is associated with adenoma recurrence, effective serodiag-nosis, and poor prognosis of CRC. Furthermore, deSUMOylation induces the nucleocytoplasmic transport of UTP18, driving cell-cycle progression and tumorigenesis via mediation of the instability of p21 mRNA. In addition, the growth and ribosome biogenesis of adenoma organoids is found to be promoted by overex-pression of UTP18. Thus, UTP18 contributes to multiple roles in adenogenesis and malignancy of CRC, sug-gesting that it could be a potential biomarker and drug target for colorectal adenoma and cancer.