O-GlcNAcylation of progranulin promotes hepatocellular carcinoma proliferation.

Biochem Biophys Res Commun

Institute of Laboratory Medicine, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, School of Medical Technology, The First Dongguan Affiliated Hospital, Dongguan Key Laboratory of Environmental Medicine, Guangdong Medical University, Dongguan, 523000, China. Electronic address:

Published: January 2025

Progranulin (PGRN) is overexpressed and implicated in hepatocellular carcinoma (HCC) development; however, its post-translational modifications and regulatory mechanisms in HCC remain largely unexplored. Here, the expression levels of PGRN, OGT, and O-GlcNAcylation were found to be elevated in both HCC samples and cell lines. LC-MS/MS analysis and immunoprecipitation revealed that PGRN underwent O-linked N-acetylglucosamine (O-GlcNAc) modification at threonine 272 (Thr272). Co-immunoprecipitation and confocal microscopy confirmed the interaction and colocalization of O-GlcNAc transferase (OGT) with PGRN. Reducing O-GlcNAcylation increased the ubiquitination of PGRN, while increasing O-GlcNAcylation inhibited ubiquitination and elevated PGRN stability, as measured by cycloheximide (CHX) chase experiments. This regulation of PGRN stability was directly linked to its expression levels. Moreover, mutation at the primary O-GlcNAc site Thr272 inhibited the activity of the PI3K/AKT/mTOR signaling pathway and suppressed HCC cell proliferation. Together, our findings indicate that O-GlcNAcylation at Thr272 is essential for PGRN-driven HCC cell proliferation.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2024.151150DOI Listing

Publication Analysis

Top Keywords

hepatocellular carcinoma
8
expression levels
8
pgrn stability
8
hcc cell
8
cell proliferation
8
pgrn
7
o-glcnacylation
5
hcc
5
o-glcnacylation progranulin
4
progranulin promotes
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!