LAR1 activates NF-κB signaling pathway by binding to APOC1 mRNA and enhancing its expression: a novel mechanism underlying breast carcinogenesis

Breast cancer (BC) remains a leading cause of cancer-related mortality in women worldwide. Through online data mining, we identified the significant upregulation of the RNA-binding protein La Ribonucleoprotein 1 (LAR1) in BC. Functionally, LAR1 knockdown impeded S-phase entry, migration, and invasion of BC cells in vitro . Consistently, it markedly suppressed tumor growth and liver metastasis in BALB/c nude mice. Mechanistically, LAR1 promoted AKT phosphorylation and IκBα degradation, leading to NF-κB activation, with the NF-κB inhibitor PDTC rescuing LAR1's effects. Integrated analysis of transcriptome and previous data of LAR1-mRNA interactome revealed Apolipoprotein C1 (APOC1) as a key target. LAR1 bound to the APOC1 3'-UTR to stabilize its mRNA, and APOC1 overexpression counteracted the effects of LAR1 knockdown. In conclusion, our study defines the LAR1-APOC1-NF-κB axis as a crucial driver of BC progression, offering a promising therapeutic strategy for BC treatment.