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Attenuation of enoyl coenzyme A hydratase short chain 1 expression in gastric cancer cells inhibits cell proliferation and migration in vitro

Abstract

Enoyl coenzyme A hydratase short chain 1 (ECHS1) is an important part of the mitochondrial fatty acid β-oxidation pathway. Altered ECHS1 expression has been implicated in cancer cell proliferation. This study assessed ECHS1 expression in human gastric cancer cell lines and investigated the effects of ECHS1 knockdown on gastric cancer cell proliferation and migration. The human gastric cancer cell lines SGC-7901, BGC-823 and MKN-28, and the immortalized human gastric epithelial mucosa GES-1 cell line were analyzed for ECHS1 protein levels using western blot. The effectiveness of ECHS1-RNA interference was also determined using western blot. Proliferation and migration of the siECHS1 cells were respectively measured with the CCK-8 and transwell assays. Phosphorylation of PKB and GSK3β was assessed using western blot. ECHS1 protein levels were significantly higher in poorly differentiated cells than in well-differentiated cells and immortalized gastric epithelial mucosa cells. Stable expression of ECHS1 shRNA was associated with an over 41% reduction in the ECHS1 protein levels of siECHS1 cells. Constitutive knockdown of the ECHS1 gene in siECHS1 cells was associated with significantly inhibited cell proliferation and migration. We also observed decreased levels of PKB and GSK3β phosphorylation in siECHS1 cells. ECHS1 expression is increased in human gastric cancer cells. Increased ECHS1 expression activates PKB and GSK3β by inducing the phosphorylation of the two kinases. ECHS1 may play important roles in gastric cancer cell proliferation and migration through PKB- and GSK3β-related signaling pathways.

Abbreviations

CCK-8:

cell counting kit-8

DMEM:

Dulbecco’s modified Eagle’s medium

ECHS1:

enoyl coenzyme A hydratase short chain 1

EDTA:

ethylenediaminetetraacetic acid

FBS:

fetal bovine serum

GSK3β:

glycogen synthase kinase 3β

PKB:

protein kinase B

STAT3:

signal transducer and activator of transcription 3

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Correspondence to Xiao-San Zhu or Yi-Chen Dai.

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Zhu, XS., Gao, P., Dai, YC. et al. Attenuation of enoyl coenzyme A hydratase short chain 1 expression in gastric cancer cells inhibits cell proliferation and migration in vitro. Cell Mol Biol Lett 19, 576–589 (2014). https://doi.org/10.2478/s11658-014-0213-5

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  • DOI: https://doi.org/10.2478/s11658-014-0213-5

Keywords

  • ECHS1
  • PKB
  • GSK3β
  • Gastric cancer
  • Cell proliferation
  • Cell migration
  • Interference
  • β-oxidation pathway
  • Signaling pathways
  • Cells