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The DIAPH3/RPL6 axis regulates the cGAS-STING pathway in pancreatic cancer

Haoyang Huang1, Chao Lin1, Cheng Zhou1

  • 1Department of Acute Care Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.

European Journal of Medical Research
|November 29, 2025
PubMed

Insights

Ribosomal protein L6 (RPL6) activates the cGAS-STING pathway in pancreatic cancer cells, boosting immune responses. This RPL6-mediated immune signaling offers a potential therapeutic target for pancreatic cancer treatment.

Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is crucial for anti-tumour immunity.
  • Mechanisms regulating cGAS-STING pathway activation in pancreatic cancer are not well understood.

Purpose of the Study:

  • To investigate the role of ribosomal protein L6 (RPL6) in activating the cGAS-STING pathway in pancreatic cancer.
  • To explore the therapeutic potential of targeting the RPL6-mediated pathway in pancreatic cancer.

Main Methods:

  • Investigated the interaction between RPL6 and cGAS in pancreatic cancer cells.
  • Analyzed public databases for correlations between RPL6 expression and immune cell infiltration.
  • Assessed the impact of RPL6 overexpression on interferon-β production.
  • Examined the role of DIAPH3 and OTUD4 in regulating RPL6 protein levels.

Main Results:

  • RPL6 directly interacts with cGAS, initiating cGAS-STING signaling in pancreatic cancer cells.
  • Higher RPL6 abundance correlates with increased immune cell infiltration in pancreatic tumours.
  • Forced expression of RPL6 enhances interferon-β production in pancreatic cancer cells.
  • DIAPH3 reduces RPL6 levels by interfering with its interaction with OTUD4.

Conclusions:

  • RPL6 is a key activator of the cGAS-STING pathway in pancreatic cancer, influencing anti-tumour immune responses.
  • The RPL6-cGAS-STING axis represents a promising therapeutic target for enhancing immune control in pancreatic cancer.
Keywords:
DIAPH3OTUD4RPL6Tumor immune microenvironmentcGAS

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