USP12 stabilizes TBC1D22A via deubiquitination to activate PI3K-AKT-mTOR signaling and promote ovarian cancer progression
Year: 2026
Type: conference-abstract
Abstract: TBC1 domain family member 22A (TBC1D22A) functions as a Rab GTPase-activating protein (GAP), and its specific oncogenic mechanisms as well as upstream regulatory pathways in ovarian cancer (OC) have not been reported. We identified ubiquitin-specific protease 12 (USP12) as a novel TBC1D22A-interacting deubiquitinase via LC-MS/MS screening, co-immunoprecipitation and immunofluorescence co-localization assays. Cycloheximide chase, proteasome inhibition and in vivo ubiquitination assays were applied to verify the deubiquitination-mediated stabilization mechanism. Gain and loss-of-function plus rescue experiments were performed to evaluate OC cell proliferation, migration, invasion and downstream PI3K-AKT-mTOR signaling, with subcutaneous xenograft models for in vivo validation. Transcriptomic analysis, tissue microarrays and TCGA cohorts were used to assess expression correlation and prognostic value. USP12 stabilized TBC1D22A at the post-translational level by suppressing ubiquitin-mediated proteasomal degradation, without altering its transcription. USP12 promoted OC cell proliferation, migration and invasion in a TBC1D22A-dependent manner, in association with activation of the PI3K-AKT-mTOR pathway. Clinically, USP12 was upregulated in OC tissues, positively correlated with TBC1D22A, and predicted poor overall and progression-free survival. Our findings identified USP12 as a novel deubiquitinase of TBC1D22A, and the USP12–TBC1D22A axis may serve as a promising therapeutic target for OC.
Authors: Xiaofeng Lv, Ruyue Gong, Xintong Cai, Ruixia Guo
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,890
OpenAlex ID: W7220693228