Regulatory mechanism of fatty acid‑CoA metabolic enzymes under endoplasmic reticulum stress in lung cancer

Liu,Kuan‑Ting; Yeh,I‑Jeng; Chou,Shih‑Kai; Yen,Meng‑Chi; Kuo,Po‑Lin

doi:10.3892/or.2018.6664

Regulatory mechanism of fatty acid‑CoA metabolic enzymes under endoplasmic reticulum stress in lung cancer

Authors:
- Kuan‑Ting Liu
- I‑Jeng Yeh
- Shih‑Kai Chou
- Meng‑Chi Yen
- Po‑Lin Kuo
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Affiliations: Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan, R.O.C., Department of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan, R.O.C., Graduate Institute of Medicine, College of Medicine, Kaohsiung 807, Taiwan, R.O.C., Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan, R.O.C.
Published online on: August 21, 2018 https://doi.org/10.3892/or.2018.6664
Pages: 2674-2682

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Abstract

The endoplasmic reticulum (ER) is an organelle involved in various physiological processes such as lipid metabolism, protein synthesis and folding, and cellular calcium storage. In a physiological tumor microenvironment, hypoxia, nutrient deprivation, and calcium dysregulation cause accumulation of unfolded and misfolded proteins. Such accumulation induces ER stress and unfolded protein responses (UPRs). Increased UPR signaling pathways are associated with multiple types of cancer. The influence of ER stress on acyl‑CoA metabolic enzymes is not well understood. Evaluation of PRECOG and Kaplan‑Meier plotter databases in the present study suggested that high expression of acyl‑CoA thioesterase (ACOT)7, ACOT11, ACOT13, soluble carrier family 27 member A4 (SLC27A4) and SLC27A5 was associated with poor clinical outcomes. In addition, expression levels of ACOT7, ACOT11, SLC27A4 and SLC27A5 were not altered after induction of ER stress. By contrast, expression of some enzymes was decreased, such as those of long‑chain acyl‑CoA synthetase (ACSL)3, ACSL4 and SLC27A2. Fatty acid uptake capacity was suppressed in lung cancer cell lines A549 and CL1‑0 after thapsigargin treatment but intracellular reactive oxygen species levels were not suppressed. Gene enrichment and regulatory element analysis were performed; the results provided potential targets for further investigation. On the whole, our findings demonstrate the potential regulatory mechanism of high‑expression of acyl‑CoA metabolic enzymes, the biological effects of decreased enzyme expression levels, possible regulatory elements, and the interaction network involved in responses to ER stress in lung cancer.

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