AMZ2 facilitates oral squamous cell carcinoma progression via USP10-mediated deubiquitination of SF3B1 and regulation of MCL-1 alternative splicing.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a prevalent malignancy characterized by high morbidity and poor prognosis, largely due to late-stage diagnosis and limited therapeutic options. The molecular mechanisms underlying OSCC pathogenesis remain incompletely understood, necessitating further investigation to support the development of targeted treatment approaches.

METHODS: The expression of Archaelysin Family Metallopeptidase 2 (AMZ2) was evaluated in OSCC tissues and cell lines. A series of in vitro and in vivo functional experiments were conducted to assess the impact of AMZ2 on OSCC tumorigenesis and disease progression. Co-immunoprecipitation and related molecular analyses were performed to examine the interactions among AMZ2, Ubiquitin-Specific Peptidase 10 (USP10), and Splicing Factor 3B Subunit 1 (SF3B1).

RESULTS: AMZ2 expression was significantly upregulated in OSCC tissues and cells. Functional assays demonstrated that elevated AMZ2 expression enhanced cellular proliferation, invasion, and migration, while inhibiting apoptosis. Mechanistically, AMZ2 recruited the deubiquitinase USP10, which stabilized SF3B1 by removing its ubiquitin chains. The subsequent deubiquitination of SF3B1 modulated myeloid cell leukemia-1 (MCL-1) alternative splicing, resulting in an increase in anti-apoptotic isoforms and promoting OSCC progression.

CONCLUSION: AMZ2 functions as an oncogenic driver in OSCC by forming an AMZ2/USP10/SF3B1 signaling axis that regulates MCL-1 splicing and suppresses apoptosis. Targeting this axis may represent a potential therapeutic strategy to improve clinical outcomes in patients with OSCC.