O-GlcNAc Glycosylation Regulates YAP1 and Participates in the Proliferation and Invasion of Colorectal Cancer
LI Yan
LI Yuqiang
YANG Weiwei
JIANG Lei
Abstract：Objective The glycosylation of O-linked beta-N-acetylglucosamine(O-GlcNAc)and Yes-associated protein 1(YAP1),as well as their expression patterns and the mechanisms of their functions in colorectal cancer,have not yet been fully elucidated.This study aims to explore the roles of O-GlcNAc glycosylation and YAP1 glycosylation in colorectal cancer by using the TCGA database,tissue specimens,and cell lines.Methods The expression levels of O-GlcNAc and OGT proteins in colorectal tissues and adjacent tissues were detected by immunohistochemistry;the expression levels of OGT mRNA in colorectal tissues and adjacent tissues were detected by qPCR;the expression status of OGT and its impact on prognosis were understood through online analysis of the TCGA database;the inhibitory effect of OSMI-1 on O-GlcNAc glycosylation was detected by Western Blot;CCK-8 and Transwell assays were used to observe the changes in the proliferation,invasion and migration abilities of colorectal cancer cells after inhibition of O-glycosylation;the expression status of YAP1 and its O-glycosylation sites were analyzed through the database,and YAP1 was determined to have undergone O-glycosylation modification by mass spectrometry analysis;the binding relationship between YAP1 and OGT was verified by Co-IP and immunofluorescence experiments;the changes in the expression location of YAP1 and the expression of downstream effect genes after inhibition of O-GlcNAc glycosylation were clarified by qPCR and immunofluorescence.Results The study found that the expression levels of OGT protein and mRNA were significantly increased in colorectal tissues,but they had no significant impact on the prognosis of patients;OSMI-1 can inhibit the O-GlcNAc glycosylation of intestinal cancer cells and also inhibit cell proliferation,invasion and migration abilities;YAP1 can bind to OGT and undergo O-GlcNAc glycosylation.When O-glycosylation is inhibited,the number of YAP1 entering the nucleus decreases and its transcriptional activity reduces.Conclusion In colorectal cancer,the level of O-GlcNAc glycosylation shows an increasing trend.OGT and YAP1 bind together,causing O-glycosylation modification of YAP1 and enhancing its transcriptional activity.
Keywords：colorectal cancerO-linked beta-N-acetylglucosamineyes-associated protein 1proliferationinvasion
Publication Date：2025-08-30
Online Publishing Date：2025-10-17(First online date of this platform, not the publication date of the document)
Pages：6( 19-24 )