FAM188B promotes progression of hepatocellular carcinoma by regulating YAP/TAZ via interaction with USP10.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and its incidence and mortality rates remain high. Therefore, new diagnostic and therapeutic approaches are urgently required. Family with sequence similarity 188 member B (FAM188B) encodes an evolutionarily conserved protein that is highly expressed in various cancers. While FAM188B has been implicated in the progression of several tumors, its role in HCC progression remains unknown. METHODS: We analyzed FAM188B expression in HCC using The Cancer Genome Atlas (TCGA) and The University of Alabama at Birmingham Cancer data analysis Portal (UALCAN) databases. Functional studies included in vitro proliferation, migration, and invasion assays, as well as in vivo xenograft models. Co-immunoprecipitation (Co-IP), Western blotting, and immunofluorescence were used to investigate the FAM188B-Ubiquitin-specific peptidase 10 (USP10)-Yes-associated protein/Transcriptional coactivator with PDZ-binding motif (YAP/TAZ) interaction. RESULTS: FAM188B was found highly expressed in HCC cells and associated with poor prognosis. Both in vitro and in vivo, FAM188B promoted the proliferation, migration, and invasion of HCC. FAM188B directly interacts with and stabilizes USP10 and the downregulation of FAM188B by shRNA led to decreased USP10 and YAP/TAZ protein levels, suggesting that FAM188B may regulate the YAP/TAZ pathway through its interaction with USP10. CONCLUSION: Our findings reveal that FAM188B plays a crucial role in enhancing HCC cell proliferation, migration, and invasion, primarily through regulating the USP10/YAP/TAZ signaling axis, which was validated in vitro and in vivo.