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

Abstract

Colorectal cancer (CRC) often develops slowly from adenoma, but the underlying mechanism remains unclear, 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 progression of colorectal adenoma to carcinoma and is associated with adenoma recurrence, effective serodiagnosis, 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 overexpression of UTP18. Thus, UTP18 contributes to multiple roles in adenogenesis and malignancy of CRC, suggesting that it could be a potential biomarker and drug target for colorectal adenoma and cancer.

• Authors: Meng Pan, Tixian Xiao, Lai Xu, Yong Xie, Wei Ge
• Journal: Cell reports (Cell Rep) Vol. 42 Issue 5 Pg. 112423 (05 30 2023) ISSN: 2211-1247 [Electronic] United States
• PMID: 37086406 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Topics

• Humans
• Colorectal Neoplasms (genetics, pathology)
• Cell Transformation, Neoplastic
• Carcinoma (genetics)
• Ribosomes (metabolism)
• Adenoma (genetics, pathology)
• Disease Progression