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Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer
Published on: August 2, 2024
TRIM27 promotes ovarian cancer progression through destabilizing AMPK and thus inactivating the cGAS/STING signaling
Liyan Wang1, Huailiang Wu2, Jing Wang1
1Department of Gynecology, Renmin hospital of Wuhan university, Wuhan 430060, China.
Abstract:
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.
Insights
Tripartite motif-containing 27 (TRIM27) drives ovarian cancer (OV) by suppressing immune surveillance. Inhibiting TRIM27 reduces cancer growth and may offer a new therapeutic target for this malignancy.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Ovarian cancer (OV) is a deadly gynecologic malignancy with poor prognosis due to late diagnosis and treatment resistance.
- Tripartite motif-containing 27 (TRIM27), a regulator in cancers, has an underexplored role in OV.
- Understanding TRIM27's function is crucial for developing novel OV therapies.
Purpose of the Study:
- To investigate the role and mechanism of TRIM27 in ovarian cancer.
- To determine if TRIM27 expression correlates with clinical outcomes in OV patients.
- To explore TRIM27 as a potential prognostic biomarker and therapeutic target for OV.
Main Methods:
- Analysis of TRIM27 expression in OV tissues and cell lines.
- Gain- and loss-of-function assays to assess TRIM27's impact on OV cell behavior.
- RNA sequencing, immunoprecipitation, mass spectrometry, and in vivo ubiquitination assays to elucidate molecular mechanisms.
- Correlation analysis between TRIM27 expression and clinical outcomes.
Main Results:
- TRIM27 is significantly upregulated in ovarian cancer tissues and cell lines.
- TRIM27 depletion inhibits OV cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition (EMT).
- TRIM27 acts as a ubiquitin ligase, degrading AMPKα via K48-linked ubiquitination, suppressing the cGAS-STING signaling pathway and immune surveillance.
- Elevated TRIM27 expression is linked to poor clinical outcomes in OV patients.
Conclusions:
- TRIM27 is an oncogenic driver in ovarian cancer, promoting tumorigenesis by evading immune surveillance.
- TRIM27 functions by mediating AMPKα degradation and suppressing the cGAS-STING pathway.
- TRIM27 represents a promising prognostic biomarker and therapeutic target for ovarian cancer.
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