MIR99AHG suppresses lung cancer progression by restricting SCD1-dependent lipid biogenesis

Long non-coding RNAs (lncRNAs) are important regulators of tumor progression, but their roles in lipid metabolic reprogramming remain incompletely defined. Here, we identified MIR99AHG as a downregulated lncRNA in lung cancer. Functional assays showed that MIR99AHG knockdown promoted, whereas MIR99AHG overexpression inhibited, cell proliferation, colony formation, migration and invasion. Mechanistically, RNA pulldown followed by mass spectrometry identified SCD1 as a MIR99AHG -associated protein. MIR99AHG depletion did not markedly alter SCD1 mRNA levels, but increased SCD1 protein fluorescence intensity, suggesting post-transcriptional regulation. Functionally, SCD1 knockdown reversed MIR99AHG depletion-induced lipid accumulation, triglyceride production, cell growth, migration and invasion. Together, these findings reveal a MIR99AHG -SCD1 regulatory axis that suppresses lipid biogenesis and malignant progression in lung cancer.