AUTHOR=Zhu Yufeng , He Qianru , Qi Ming 

TITLE=Exosomal circPTPRK promotes angiogenesis after radiofrequency ablation in hepatocellular carcinoma

JOURNAL=Experimental Biology and Medicine

VOLUME=Volume 249 - 2024

YEAR=2024

URL=https://www.ebm-journal.org/journals/experimental-biology-and-medicine/articles/10.3389/ebm.2024.10084

DOI=10.3389/ebm.2024.10084

ISSN=1535-3699

ABSTRACT=Radiofrequency ablation (RFA) is a crucial treatment for hepatocellular carcinoma (HCC), but the recurrence rate remains high due to the angiogenesis in residual cancer. We used thermal stimulation to simulate the post-RFA microenvironment. The expression profile of circRNAs between normal control HCC cell-derived exosomes and exosomes after heat stimulation were analyzed by RNA sequencing. Quantitative real-time PCR was applied to evaluate the expression of circPTPRK in exosomes and human umbilical vein endothelial cells (HUVECs). Then unveiled the functions of heat-stimulated HCC cell-derived exosomes and exosomal circPTPRK on HUVECs. Transcriptome sequencing was utilized to determine targeted genes. Heat-stimulated HCC cell-derived exosomes augmented cell proliferation, migration and angiogenesis of HUVECs. In total, 229 differentially expressed circRNAs were obtained, including 211 upregulated circRNAs and 18 downregulated circRNAs in heat-stimulated HCC cell-derived exosomes. The expression of circPTPRK was remarkably increased in heat-stimulated HCC cell-derived exosomes and the HUVECs incubated with them. Heat-stimulated HCC cell-derived exosomes with circPTPRK knockdown significantly inhibited cell proliferation, migration and angiogenesis of HUVECs. Mechanistic studies indicated that PLA2G4E as a downstream target of circPTPRK, and PLA2G4E overexpression reversed the inhibitory effect of circPTPRK knockdown on HUVEC angiogenesis. Our results indicated that exosomal circPTPRK activated HUVEC angiogenesis by upregulating PLA2G4E expression.