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BRIP1-mediated RINT1 acetylation and NF-κB activation promote DNA repair and immunosuppressive microenvironment in lung adenocarcinoma - PubMed

4 hours ago
  • #Lung adenocarcinoma
  • #Immunosuppression
  • #BRIP1
  • BRIP1 is upregulated in lung adenocarcinoma (LUAD) and correlates with poor prognosis.
  • BRIP1 promotes LUAD cell proliferation, invasion, and DNA repair via homologous recombination (HR).
  • BRIP1 enhances RINT1 acetylation, strengthening RINT1-RAD50 interaction and MRE11-RAD50-NBS1 complex assembly.
  • BRIP1 suppresses cGAS-STING innate immune activation by limiting cytosolic DNA accumulation.
  • BRIP1 activates NF-κB signaling via ALKBH5 interaction, upregulating PD-L1 and promoting metastasis.
  • BRIP1-high tumors exhibit an immune-cold microenvironment with regulatory T-cell enrichment and cytotoxic T-cell exclusion.
  • BRIP1 overexpression confers resistance to PD-L1 blockade, which can be reversed by combining anti-PD-L1 therapy with STING activation.