USP43 drives cervical carcinoma progression through regulation of the Hippo/TAZ pathway

Cervical carcinoma (CC) poses significant health challenges, with its pathogenesis not fully understood. While ubiquitin specific peptidase 43 (USP43) is implicated in various cancers, its role in CC and regulation of the Hippo/Transcriptional Co-Activator With PDZ-Binding Motif (TAZ) pathway remain unexplored. This study examines USP43's impact on CC progression and its interaction with TAZ.

USP43 expression levels in CC tissues and cell lines were assessed using reverse transcription real-time polymerase chain reaction (RT-qPCR) and Western blot. The effects of USP43 silencing on cell proliferation, migration, and invasion were evaluated through cell counting Kit-8 (CCK-8), 5-ethynyl-2'deoxyuridine (EdU), colony formation, and transwell assays. Immunofluorescence staining and co-immunoprecipitation (Co-IP) assays were used to explore the interaction between USP43 and TAZ. Polyubiquitination assays were performed to evaluate ubiquitination and stability of TAZ, and cycloheximide (CHX) chase experiments determined the half-life of TAZ. In vivo studies using BALB/c nude mice examined the impact of USP43 knockdown on tumor growth and metastasis.

USP43 was overexpressed in CC tissues and cell lines. Silencing of USP43 reduced cell proliferation, migration, invasion, and the epithelial-mesenchymal transition (EMT) process. Co-IP and ubiquitination assays revealed that USP43 interacted with and stabilized TAZ by inhibiting TAZ ubiquitination. CHX chase experiments confirmed that USP43 prolonged TAZ protein stability. In vivo, USP43 knockdown led to reduced tumor growth and lung metastasis. Overexpression of TAZ reversed the inhibitory effects of USP43 silencing on CC cell proliferation, migration, invasion and EMT CONCLUSION: USP43 promotes CC cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition (EMT) by activating the Hippo/TAZ pathway. These findings enhance our understanding of USP43's role in CC progression and highlight potential therapeutic targets for the treatment of CC.