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.

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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