Coke Oven Emission Exposure Triggers Malignant Transformation of Lung Epithelial Cells by -Dependent Alteration of Acetyl-CoA Metabolism.

Exposure to coke oven emissions (COEs) is an important environmental factor in lung cancer. A previous study revealed that 20 μg/mL COE exposure for 120 days could induce malignant transformation of lung epithelial cells. However, the underlying mechanism remains unclear. The epigenetic regulation of long noncoding RNAs (lncRNAs) plays an important role in carcinogenesis. Changes in lncRNA expression during COE-induced malignant transformation were detected, highlighting the importance of gene-environment interactions in cancer. Here, we identified that was downregulated in COE-induced malignant transformation of lung epithelial cells. Interestingly, this reduction was found to have a gradient effect on different stages of cells of COE exposure. Moreover, we found that downregulation of expression in lung cancer was related to patients' poor prognosis. Phenotypic studies have demonstrated that suppressed lung cancer cell proliferation in vitro and in vivo. Further mechanistic studies revealed that directly interacts with ACSS2, an important enzyme responsible for synthesizing acetyl-CoA, leading to abnormal acetyl-CoA metabolism and affecting COE-induced lung carcinogenesis. COE-induced malignant transformed cells or cells with the knockdown of showed significantly increased fatty acid and cholesterol levels, while normal lung epithelial cells or cells with overexpression of showed substantially decreased fatty acid and cholesterol levels. Moreover, transfection of ACSS2 into cells with overexpressing could rescue the induced cell phenotype. Our findings link regulated acetyl-CoA metabolism with COE-induced malignant transformation and imply that could be an important biomarker for early intervention and diagnosis of lung cancer.