BICDL1 Mediates Pyroptosis to Promote Breast Cancer Cell Proliferation,Inhibition,and Migration

Abstract

Elevated levels of Bicaudal-D Family Like Cargo Adaptor 1 (BICDL1) are associated with poor prognosis in various cancers. However, the role of BICDL1 in breast cancer (BC) has not been reported. We analyzed BICDL1 expression in BC using bioinformatics and molecular experiments. Gene Set Enrichment Analysis was conducted to identify significantly enriched signaling pathways related to BICDL1. The effects of BICDL1 on BC cell proliferation, migration, invasion, and expression of epithelial-mesenchymal transition (EMT)-related proteins were assessed using colony formation assays, Transwell assays, and Western blot. The influence of BICDL1 on pyroptosis in BC cells was determined by measuring the expression of key pyroptosis proteins (NLRP3, GSDMD-N, procaspase-1, cleaved caspase-1, ASC), lactate dehydrogenase release, and cytokines (IL-1β and IL-18). We also investigated whether BICDL1 promotes BC proliferation and metastasis by regulating pyroptosis using Nigericin, an agent that induces NLRP3 inflammasome activation. The results showed that BICDL1 was significantly overexpressed in BC tissues and cells. Knockdown of BICDL1 inhibited BC cell proliferation, migration, invasion, and the EMT process, while overexpression of BICDL1 had the opposite effects. BICDL1 was enriched in the pyroptosis pathway; overexpression of BICDL1 suppressed pyroptosis, thus promoting BC cell proliferation, inhibition, and migration. Notably, the addition of Nigericin reversed the effects of BICDL1 overexpression on BC cells. These results suggested that BICDL1 promoted BC cell proliferation, inhibition, and migration by hindering pyroptosis. These findings indicate that BICDL1 is a potential biomarker for BC treatment.