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

Abstract

Abstract. 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 β-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)3β 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 GSK3β-associated signaling pathways.

Remodelin, a N‐acetyltransferase 10 (NAT10) inhibitor, alters mitochondrial lipid metabolism in cancer cells

“…Notably, both MFAE and MBO pathways possess ECHS1 (Figures 3 and 4). Studies involving the knockdown of ECHS1 have shown that this gene is involved in cancer cell survival, cell proliferation and metastasis 22,23 …”

“…Studies involving the knockdown of ECHS1 have shown that this gene is involved in cancer cell survival, cell proliferation and metastasis. 22,23…”

ECHS1, an interacting protein of LASP1, induces sphingolipid-metabolism imbalance to promote colorectal cancer progression by regulating ceramide glycosylation

“…ECHS1 is a key enzyme that catalyzes the second step of the β-oxidation pathway in fatty-acid metabolism. Apart from its critical roles in regulating fatty acid metabolism, numerous literatures have indicated that ECHS1 might be involved in the development of tumor, including colon [ 14 , 15 ], liver [ 27 ], gastric [ 17 ], and renal [ 28 ] cancer. In CRC cell lines, it has been reported that ECHS1 is able to suppress proliferation and migration through PI3K–Akt–GSKβ signaling pathways [ 15 ], and the knockdown of ECHS1 attenuates HCC proliferation by impairing cell metabolism and inducing cell apoptosis and autophagy by activating the AMP protein kinase (AMPK) pathway [ 16 ].…”

“…Apart from its critical roles in regulating fatty acid metabolism, numerous literatures have indicated that ECHS1 might be involved in the development of tumor, including colon [ 14 , 15 ], liver [ 27 ], gastric [ 17 ], and renal [ 28 ] cancer. In CRC cell lines, it has been reported that ECHS1 is able to suppress proliferation and migration through PI3K–Akt–GSKβ signaling pathways [ 15 ], and the knockdown of ECHS1 attenuates HCC proliferation by impairing cell metabolism and inducing cell apoptosis and autophagy by activating the AMP protein kinase (AMPK) pathway [ 16 ]. Additionally, in the human gastric cancer cell lines, the protein levels of ECHS1 were significantly higher than those in nonneoplastic gastric epithelial mucosa cells [ 17 ].…”

“…The expression of ECHS1 has been identified in numerous types of cancer cells or patient tissues by gene or proteomic expression profiling. It was reported that the expression of ECHS1 was significantly increased in colorectal [ 14 , 15 ], liver [ 16 ], and gastric [ 17 ] cancers. Although evidence suggests a potential role of ECHS1 involved in tumor occurrence and development, the underlying mechanisms have not been elucidated to date.…”