NONO Protein Regulates the Immune Response in Human Triple-Negative Breast Cancer Cells.

ABSTRACT: Breast cancer (BC) remains a leading cause of cancer-related mortality worldwide, with limited treatment options for triple-negative breast cancer (TNBC). The RNA-binding protein non-POU domain-containing octamer-binding protein (NONO) has emerged as a critical regulator of tumorigenesis, but its role in immune signaling remains unexplored. We analyzed the effect of NONO protein by modulating its expression using short hairpin RNA (shRNA) and a chemical inhibitor (R)-SKBG-1. We demonstrate that NONO depletion in MDA-MB-231 TNBC cells leads to cytoplasmic DNA accumulation, micronuclei formation, and activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS/STING) pathway, resulting in enhanced modulation of the immune response. NONO-deficient cells showed increased cGAS

SUBMITTER: Iannuzzi CA 

PROVIDER: S-EPMC12429829 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature