Metabolic profiling analysis upon acylcarnitines in tissues of hepatocellular carcinoma revealed the inhibited carnitine shuttle system caused by the downregulated carnitine palmitoyltransferase 2

作者：Xin Lu, Xiaohan Zhang, Yongjian Zhang, Kun Zhang, Chao Zhan, Xiuyun Shi, Yiqun Li, Yiqun Li, Jianxiang Zhao, Yunfan Bai, Yu Wang, Huan Nie, Li Yu, Li Yu · 发表于：Molecular Carcinogenesis · 年份：2019 · DOI：10.1002/mc.22967 · 被引用次数：54 · 研究领域：Metabolism and Genetic Disorders、Metabolomics and Mass Spectrometry Studies、Peroxisome Proliferator-Activated Receptors

The carnitine shuttle system (CSS) plays a crucial role in the transportation of fatty acyls during fatty acid β-oxidation for energy supplementation, especially in cases of high energy demand, such as in cancer. In this study, to systematically characterize alterations of the CSS in hepatocellular carcinoma (HCC), acylcarnitine metabolic profiling was carried out on 80 pairs of HCC tissues and adjacent noncancerous tissues (ANTs) by using ultra-performance liquid chromatography coupled to mass spectrometry. Twenty-four acylcarnitines classified into five categories were identified and characterized between HCCs and ANTs. Notably, increased saturated long-chain acylcarnitines (LCACs) and decreased short- and medium-chain acylcarnitines (S/MCACs) were simultaneously observed in HCC samples. Subsequent correlation network and heatmap analysis indicated low correlations between LCACs and S/MCACs. The mRNA and protein expressions of carnitine palmitoyltransferase 2 (CPT2) was significantly downregulated in HCC samples, whereas CPT1A expression was not significantly changed. Correspondingly, the relative levels of S/MCACs were reduced and those of LCACs were increased in BEL-7402/CPT2-knockdown cells compared to negative controls. Both results suggested that decreased shuttling efficiency in HCC might be associated with downregulation of CPT2. In addition, decreases in the mRNA expression of acetyl-CoA acyltransferase 2 were also observed in HCC tissues and BEL-7402/CPT2-knockdown...