Attenuation of enoyl coenzyme A hydratase 1 expression in colorectal cancer cells using small interfering RNA inhibits cell proliferation and migration

摘要

Colorectal cancer is one of the most commonly diagnosed types of cancer and is a leading cause of cancer-associated mortality worldwide. Short chain enoyl coenzyme A hydratase 1 (ECHS1) is an important gene involved in the mitochondrial fatty acid -oxidation pathway. In addition, ECHS1 has been implicated in a variety of cancers, including breast, prostate, colon and liver cancer. The aim of the present study was to examine the expression of ECHS1 in the human HCT-8 colorectal cancer cell line. The results showed that ECHS1 expression was significantly increased in poorly-differentiated cells compared with that in well-differentiated cells. In order to further investigate the functions of ECHS1 in colorectal cancer cells, a stably transfected HCT-8 cell line expressing small interfering (si) RNA targeting the ECHS1 gene was established. The expression of the ECHS1 siRNA was found to reduce ECHS1 protein levels in ECHS1-silenced cells by 40%. Cell proliferation and cell migration of the siECHS1 cells were characterized using Cell Counting Kit-8 and Transwell assays, respectively, the results of which showed that the constitutive knockdown of the ECSH1 gene in HCT-8 cells significantly inhibited cell proliferation and migration. Furthermore, decreased levels of Akt and glycogen synthase kinase (GSK)3 phosphorylation were observed in ECHS1-silenced HCT-8 cells compared with that of parental or pU6 empty vector-transfected cells. In conclusion, the results of the present study suggested that ECHS1 may have an important role in colorectal cancer cell proliferation and migration via activation of Akt- and GSK3-associated signaling pathways.