Malic enzyme 2 promotes the progression of hepatocellular carcinoma via increasing triglyceride production

• Published in: Cancer medicine (Malden, MA) Vol. 10; no. 19; pp. 6795 - 6806
• Main Authors: Zhang, Shuai, Cheng, Zhi‐Mei, Yu, Jia‐LI, Lu, Kai, Xu, Sheng‐Jie, Lu, Yuan, Liu, Ting, Xia, Bai‐Juan, Huang, Zhi, Zhao, Xu‐Ya, He, Wei, Li, Jun‐Xiang, Cao, Wei, Huang, Yu, Wang, Ling, Zeng, Zhu, Zou, Xun, Liu, Rong, Zhang, Yu‐Sui, Wu, Xiao‐Ping, Jiang, Tian‐Peng, Zhou, Shi
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.10.2021; John Wiley and Sons Inc; Wiley
• Subjects: Animals; Antibodies; Apoptosis; Cancer Biology; Carcinogenesis; Carcinoma, Hepatocellular - mortality; Carcinoma, Hepatocellular - physiopathology; Cell cycle; Cell growth; Cell Line, Tumor; Cell migration; Cell Proliferation; Disease Progression; Enzymes; Female; HCC; Hepatocellular carcinoma; Humans; Liver cancer; Liver Neoplasms - mortality; Liver Neoplasms - physiopathology; Lung cancer; Malate Dehydrogenase - adverse effects; Male; Malic enzyme; ME2; Medical prognosis; Metabolism; Mice; Mice, Nude; migration; Survival Analysis; Transcription; triglyceride; Triglycerides - adverse effects; Tumorigenesis; Tumors; Xenografts; triglyceride; migration; HCC; ME2; tumorigenesis
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.4209

The incidence and mortality of hepatocellular carcinoma (HCC) are gradually increasing during the past years. Recently, some studies have reported that malic enzyme (ME) plays an important role in cancer development, while the involvement of ME2 in HCC remains still undetermined. Here, we demonstrated that ME2 played an oncogenic role in HCC. ME2 was overexpressed in HCC tissues. TCGA database showed that the ME2 transcript level was inversely associated with the survival of HCC patients. Loss‐of‐function and gain‐of‐function assays showed that ME2 promoted HCC cell growth and migration. Furthermore, the xenografted tumorigenesis of MHCC97H cells was retarded by ME2 knockdown. ME2 silencing also suppressed the cell cycle process and induced apoptosis. Mechanistically, ME2 potentiated triglyceride synthesis, inhibition of which suppressed the proliferation and migration. We propose that ME2 promotes HCC progression by increasing triglyceride production. The expression of ME2 was significantly elevated in HCC tissues.ME2 promotes HCC progression by increasing triglyceride production.