TY  - EJOU
AU  - Xu, Guo-Zhi 
AU  - Guan, Han-Yang 
AU  - Guo, Yan-Guan 
AU  - Zhang, Yi-Ran 
AU  - Pan, Jing-Hua 
AU  - Luo, Simin 
AU  - Ding, Hui 
AU  - Pan, Yunlong 
AU  - Yao, Qi 

TI  - USP13 Suppresses Colorectal Cancer Angiogenesis by Downregulating VEGFA Expression through Inhibition of the PTEN-AKT Pathway
T2  - Oncology Research

PY  - 2025
VL  - 33
IS  - 8
SN  - 1555-3906

AB  -  <b>Background:</b> Tumor angiogenesis is related to solid tumor occurrence. Ubiquitin-specific peptidase 13 (USP13) is a deubiquitinating enzyme with a pivotal effect on tumor proliferation, metastasis, and tumorigenesis. Nonetheless, its effect on colorectal cancer (CRC) angiogenesis remains poorly understood. <b>Methods:</b> Human umbilical vein endothelial cells (HUVECs) and CRC cells were cultivated, followed by USP13 knockdown/overexpression using shRNA lentiviral vectors or plasmids. Conditioned media (CM) from treated CRC cells were collected to assess HUVEC migration, invasion, and tube formation. Phosphatase and tensin homolog (PTEN) overexpression and recombinant vascular endothelial growth factor A (VEGFA) rescue experiments were performed. Molecular mechanisms were analyzed via Western blot (PTEN, p-AKT, VEGFA), co-immunoprecipitation (PTEN ubiquitination), and <i>in vivo</i> nude mice study to detect the role of USP13 in tumor angiogenesis. <b>Results:</b> USP13 expression in CRC cells is downregulated and negatively related to platelet endothelial cell adhesion molecule-1 (CD31) expression. Furthermore, the conditioned medium from CRC cells with USP13 knockdown significantly promoted HUVEC migration, invasion, and tube formation, while USP13 overexpression exerted the opposite effect. Additionally, USP13 overexpression significantly increased PTEN expression while decreasing protein kinase B (AKT) phosphorylation levels. Concurrently, USP13 overexpression significantly reduced PTEN ubiquitination, whereas USP13 knockdown remarkably increased this modification. Overexpression of PTEN in sh-USP13 CRC cells decreased the expression levels of VEGFA and p-AKT. USP13 also inhibited tumor angiogenesis through downregulating VEGFA, and recombinant VEGFA blocked the inhibition of the conditioned medium from USP13-overexpressing CRC cells against HUVEC angiogenesis <i>in vivo</i>. <b>Conclusions:</b> USP13 downregulated VEGFA and inhibited tumor angiogenesis via the PTEN-AKT pathway.
KW  - Colorectal cancer (CRC); angiogenesis; ubiquitin-specific peptidase 13 (USP13); Vascular Endothelial Growth Factor A (VEGFA)

DO  - 10.32604/or.2025.060440