Nonsmall cell lung cancer (NSCLC), which constitutes 85%−90% of lung cancer (LC) cases, is among the most frequently diagnosed malignancies. Peroxisome proliferator-activated receptor γ coactivator 1 α (PPARGC1A, also known as PGC-1α) has emerged as a major modulator of mitochondrial formation and energy expenditure, and serves critical functions in a range of malignancies. Nevertheless, its clinicopathological significance and biological function in the development of NSCLC remain obscure. This investigation revealed that PGC-1α expression exhibited elevated levels in LC. Moreover, enhanced PGC-1α expression augmented the oncogenic potential of NSCLC cells, whereas the downregulation of PGC-1α inhibited the proliferative and migrative capability and suppressed tumor growth in vivo. Mechanistically, PGC-1α interacted with forkhead box protein M1 (FOXM1), a commonly known transcription factor, and enhanced its transcriptional activation of downstream target mucin-1 (MUC1). The ectopic expression of MUC1 could reverse the inhibitory impact of PGC-1α depletion on the proliferation of NSCLC cells. Overall, the data suggested that targeting PGC-1α suppresses NSCLC progression through the FOXM1/MUC1 pathway and potentially offers a novel therapeutic approach for NSCLC treatment.
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