Lysophosphatidylcholine inhibits lung cancer cell proliferation by regulating fatty acid metabolism enzyme long‐chain acyl‐coenzyme A synthase 5

Abstract Lung cancer is a widespread malignancy with a high death rate and disorder of lipid metabolism. Lysophosphatidylcholine (lysoPC) has anti‐tumour effects, although the underlying mechanism is not entirely known. The purpose of this study aims at defining changes in lysoPC in lung cancer patients, the effects of lysoPC on lung cancer cells and molecular mechanisms. Lung cancer cell sensitivity to lysoPC was evaluated and decisive roles of long‐chain acyl‐coenzyme A synthase 5 (ACSL5) in lysoPC regulation were defined by comprehensively evaluating transcriptomic changes of ACSL5‐downregulated epithelia. ACSL5 over‐expressed in ciliated, club and Goblet cells in lung cancer patients, different from other lung diseases. LysoPC inhibited lung cancer cell proliferation, by inducing mitochondrial dysfunction, altering lipid metabolisms, increasing fatty acid oxidation and reprograming ACSL5/phosphoinositide 3‐kinase/extracellular signal‐regulated kinase‐regulated triacylglycerol‐lysoPC balance. Thus, this study provides a general new basis for the discovery of reprogramming metabolisms and metabolites as a new strategy of lung cancer precision medicine.