USP39 Depletion Plays Repressive Roles in Laryngeal Squamous Cell Carcinoma Development

Abstract

Laryngeal squamous cell carcinoma (LSCC) is a prevalent malignant tumor of the upper respiratory tract. Ubiquitin-specific protease 39 (USP39) has been identified as an oncogenic regulator in various malignant tumors; however, its specific roles in LSCC remain unexplored. In this study, immunohistochemistry was employed to assess USP39 expression in LSCC tissues and adjacent normal tissues. Subsequently, a USP39 knockdown cellular model was established to investigate its effects on cell proliferation, apoptosis, and migration through Celigo cell counting, colony formation, flow cytometry, and transwell assays, respectively. A tumor-bearing animal model was established to verify the impact of USP39 on LSCC In Vivo. Co-immunoprecipitation (Co-IP) assay was used to validate protein–protein interaction. Our results suggested that USP39 was highly expressed in laryngeal cancer tissues, which exhibited a correlation with lymphatic metastasis. In Vitro loss-of-function experiments revealed that depletion of USP39 suppressed cell proliferation and migration, and induced apoptosis in LSCC cells. Furthermore, silencing USP39 restrained tumor growth silencing USP39 In Vivo. Mechanistically, USP39 was found to interact with and upregulated Aurora kinase B (AURKB). AURKB depletion attenuated the protumorigenic effects of USP39 overexpression. Additionally, USP39 enhanced ERK1/2 phosphorylation, and pharmacological inhibition of ERK1/2 abrogated USP39-driven proliferative and clonogenic capacities. In summary, this study underscores the significance of USP39 in the development of LSCC, positioning it as a promising therapeutic target for LSCC treatment.