TRIM27 promotes ovarian cancer progression through destabilizing AMPK and thus inactivating the cGAS/STING signaling pathway
Ovarian cancer (OV) is a highly malignant gynecologic malignancy with a poor prognosis, primarily due to late-stage diagnosis and therapeutic resistance. Tripartite motif-containing 27 (TRIM27), a member of the TRIM protein family, acts as a bifunctional regulator in various cancers. However, its role in OV remains underexplored. This study demonstrated that TRIM27 is significantly upregulated in OV tissues and cell lines. Functional assays utilizing both gain- and loss-of-function approaches revealed that TRIM27 depletion inhibits ovarian cancer cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition (EMT). Mechanistic investigations, including RNA sequencing, immunoprecipitation, mass spectrometry, and in vivo ubiquitination assays, identified TRIM27 as a ubiquitin ligase that mediates K48-linked ubiquitination and subsequent proteasomal degradation of AMPKα, thereby suppressing the cGAS-STING signaling pathway. These results established TRIM27 as a pivotal oncogenic driver in OV through immune surveillance evasion. Additionally, elevated TRIM27 expression was associated with poor clinical outcomes, suggesting its potential as both a novel prognostic biomarker and therapeutic target for ovarian cancer.