LncRNA-CFTBS enhances Mycobacterium tuberculosis survival in macrophages by modulating ferroptosis through the...

Tuberculosis (TB) remains one of the primary global causes of death and poses substantial public health challenges. The intracellular survival of Mycobacterium tuberculosis (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.