USP25 promotes hepatocellular carcinoma progression by interacting with TRIM21 via the Wnt/β-catenin signalling pathway

Abstract

Abstract The USP25 protein has been reported to participate in the development of several cancers. However, few studies have reported its association with HCC. In our study, USP25 was highly expressed in HCC tissue and HCC cell lines. Importantly, high expression of USP25 in tissues was closely related to poor prognosis. USP25 knockdown markedly reduced the proliferation, migration and invasion of HepG2 and MHCC97H cells, whereas USP25 overexpression led to the opposite effects. In addition, we demonstrated that USP25 interacted with TRIM21 to regulate the protein levels of the EMT (E-cadherin, N-cadherin and Snail) and Wnt/β-catenin pathway (β-catenin, APC, Axin2 and GSK3β) and those of their downstream proteins (C-myc and Cyclin D1). Finally, we verified that knocking out USP25 inhibited tumour growth in vivo and promoted the distant metastasis of the tumor. In summary, our data showed that USP25 was overexpressed in HCC. USP25 promoted the proliferation, migration, invasion and EMT of HCC cells by interacting with TRIM21 to activate the β-catenin signalling pathway.