LncRNA-CFTBS enhances <i>Mycobacterium tuberculosis</i> survival in macrophages by modulating ferroptosis through the miR-515-5p/miR-519e-5p/SAT1 axis

(M.tb) can be influenced by ferroptosis; however, how lipid peroxidation-induced ferroptosis operates during M.tb infection remains unclear. Our study revealed a significantly upregulated lncRNA (lncRNA-cytoplasm-regulating ferroptosis and tuberculosis survival (CFTBS)) that modulates ferroptosis, enhancing M.tb intracellular survival by affecting the lipid peroxidation-related pathway rather than the cystine/GSH/GPX4 pathway. We elucidated that lncRNA-CFTBS competitively binds miR-515-5p and miR-519e-5p, regulating spermidine/spermine N1-acetyltransferase 1 (SAT1) expression, which plays a critical role in increasing the expression of arachidonic acid 15-lipoxygenase (ALOX15) and promoting lipid peroxidation and ferroptosis. Our findings reveal a mechanism by which lncRNA-CFTBS enhances M.tb survival during infection by regulating a noncanonical ferroptosis signalling pathway, offering a deeper understanding of the function of noncoding RNAs in ferroptosis and TB pathogenesis and identifying potential therapeutic targets.