Olaparib targets Ubiquitin D to promote autophagy in hepatocellular carcinoma by regulating glutamine metabolism
Year: 2025
Type: article
Abstract: Background To explore Ubiquitin D (UBD) and autophagy in hepatocellular carcinoma (HCC) and the key role of Olaparib targeting UBD in treating HCC.Research design and methods Bioinformatics analysis was conducted to study UBD expression in HCC tissues. qRT-PCR and Western blot measured UBD mRNA/protein levels, autophagy markers, and Gln metabolism proteins in HCC tissues. Cellular thermal shift assay (CETSA) confirmed Olaparib-UBD interaction. A xenograft tumor model was established to observe tumor growth in mice, with qRT-PCR and western blot used to measure UBD expression levels in tumor tissues and Immunohistochemistry (IHC) used to assess expression of Microtubule-associated protein light chain 3 (LC3), sequestosome 1 (P62), solute carrier family 1 member 5 (SLC1A5), and glutaminase (GLS).Results UBD was highly expressed in HCC tissues (p = 7.6e-11). UBD could negatively regulate autophagy levels by activating Gln metabolism. Olaparib could target and downregulate UBD expression, promoting HCC cell autophagy by regulating Gln metabolism pathways. Olaparib treatment in xenograft mice overexpressing UBD significantly reduced tumor growth (p < 0.05), inhibited Gln metabolism pathways, and enhanced HCC cell autophagy.Conclusions Olaparib targeted UBD to promote autophagy in HCC by inhibiting Gln metabolism pathways.
Authors: Weijun Zhu, Fangfang Zhang, Haiyan Qu, Ningjun Li, Xi Chen, Wenhui Tu
Institutions: Taizhou Municipal Hospital, Taizhou University, Taizhou University
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4415956242