title: Enoyl-coenzyme A hydratase short chain 1 silencing attenuates the proliferation of hepatocellular carcinoma by inhibiting epidermal growth factor signaling in vitro and in vivo.
abstract: Enoyl-coenzyme A hydratase short chain 1 (ECHS1) regulates fatty acid metabolism and is an essential factor in tumor development. The present study aimed to investigate the molecular mechanisms of ECHS1 in hepatocellular carcinogenesis by studying proliferation and survival in ECHS1 knocked-down hepatocellular carcinoma (HCC) cell lines, HepG2 and HuH7. The effect of ECHS1 on tumor development was investigated by tumor transplantation in nude mice, and the signaling pathways involved in the ECHS1-mediated regulation of HCC cell proliferation were identified by western blot analysis. The silencing of ECHS1 suppressed HCC cell proliferation in vitro and suppressed the growth of transplanted tumors in vivo. In addition, the phosphorylation of EGFR and its downstream effectors ERK1/2 and AKT was downregulated in ECHS1 knocked-down cells and tumor tissues. Furthermore, knockdown of ECHS1 in HCC suppressed cyclin D3 and cyclin dependent kinase 6 expression, whilst enhancing p16 and p21 expression. Therefore, ECHS1 may also be involved in cell cycle progression in HCC cells. These results suggested that ECHS1 may promote cell proliferation in HCC in an EGFR-dependent manner.
authors.affiliation: Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Department of Hepatobiliary Surgery, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian 361004, P.R. China.
authors.forename: Bi-Yun
authors.initials: BY
authors.lastname: Lin
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian 361004, P.R. China.
authors.forename: Chuan-Xing
authors.initials: CX
authors.lastname: Xiao
authors.affiliation: Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Department of Hepatobiliary Surgery, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian 361004, P.R. China.
authors.forename: Wen-Xiu
authors.initials: WX
authors.lastname: Zhao
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian 361004, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian 361004, P.R. China.
authors.forename: Xu
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian 361004, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Department of Hepatobiliary Surgery, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian 361004, P.R. China.
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Wang
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation / Q000235:genetics; D004746:Enoyl-CoA Hydratase / Q000096:biosynthesis / Q000235:genetics*; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics*; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3 / Q000096:biosynthesis; D051058:Oncogene Protein v-akt / Q000096:biosynthesis; D010766:Phosphorylation; D015398:Signal Transduction
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors; D051058:Oncogene Protein v-akt; D048052:Mitogen-Activated Protein Kinase 3; C000600529:ECHS1 protein, human; D004746:Enoyl-CoA Hydratase