Foxd3/SLC5A6 axis regulates apoptosis in LUAD cells by controlling mitochondrial biotin uptake

Abstract

Lung cancer remains one of the leading causes of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for over 85 % of cases. Lung adenocarcinoma (LUAD) is the most common subtype of NSCLC, and while targeted therapies and immune checkpoint inhibitors have improved outcomes, many patients exhibit resistance, necessitating the development of novel treatments. This study explores the role of the SLC5A6 gene, which encodes a sodium-dependent multivitamin transporter critical for mitochondrial function, in LUAD progression. We found that SLC5A6 is significantly upregulated in LUAD tissues and is associated with poor prognosis. Overexpression of SLC5A6 enhanced cell proliferation and migration, while knockout of SLC5A6 impaired these processes and induced apoptosis by disrupting mitochondrial function. Additionally, we identified Foxd3 as a key transcription factor regulating SLC5A6 expression. In vivo experiments demonstrated that SLC5A6 knockout effectively inhibited tumor growth. These findings suggest that SLC5A6 is a potential therapeutic target for LUAD, offering a new avenue for treatment strategies.