The effect of ELOVL6 fatty acid elongase inhibition on the expression of genes associated with the metastasis of breast cancer

Захарова, Г. С.; Полозников, А. А.; Астахова, Л. В.; Raigorodskaya, M. P.; Khesina, Zoya B.; Fomicheva, K. A.; Buryak, А. К.; Alekseev, B. Ya.

doi:10.1007/s11172-018-2374-2

Cited by 2 publications

(1 citation statement)

References 70 publications

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“… 32 Inhibition of ELOVL6 potentiates upregulation of genes related to breast cancer development and metastasis in vivo. 33 Additionally, in a study investigating pediatric primary central nervous system germ cell tumors, the expression of ELOVL6 was observed to be abundant in germinoma. 34 However, the GEPIA database ( http://gepia.cancer-pku.cn/ ) displayed that ELOVL6 is expressed at high level in CRC tissues.…”

Section: Discussionmentioning

confidence: 99%

Apatinib Promotes Ferroptosis in Colorectal Cancer Cells by Targeting ELOVL6/ACSL4 Signaling

Tian

Li²,

Ge³

2021

CMAR

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Background: Colorectal cancer (CRC) is a common digestive system malignancy. Ferroptosis, a new form of regulated cell death, plays a vital role in the pathogenesis and therapy of cancers. Objective: We aimed to study the role of apatinib in ferroptosis of CRC cells and its potential mechanisms. Materials and Methods: Human CRC HCT116 cells were exposed to apatinib. Cell viability was examined using a CCK-8 kit. The concentrations of intracellular iron and reactive oxygen species (ROS) were detected using kits. Additionally, Western blot analysis was used to determine the expression of ferroptosis-related proteins. Elongation of very longchain fatty acids family member 6 (ELOVL6) was one of the targets of apatinib predicted by SwissTargetPrediction. Therefore, ELOVL6 expression was evaluated after treatment with apatinib. Subsequently, the effects of ELOVL6 overexpression on ferroptosis of HCT116 cells were investigated. Finally, STRING database was applied to predict the potential proteins interacting with ELOVL6, and co-immunoprecipitation (co-IP) assay was applied for confirmation. Results: Results indicated that apatinib decreased cell viability and increased the contents of intracellular iron ROS. Moreover, significantly upregulated ACSL4 expression was observed, accompanied by notable downregulation of GPx4 and FTH1 expression after apatinib exposure. Furthermore, ELOVL6 expression was remarkably enhanced in HCT116 cells, which was dramatically inhibited under apatinib intervention. ELOVL6 overexpression reversed the effects of apatinib on cell viability and ferroptosis of HCT116 cells. Moreover, ACSL4, a vital regulator of ferroptosis, could interact with ELOVL6 directly, which was confirmed by the result of co-IP. Conclusion: These findings demonstrated that apatinib promoted ferroptosis in CRC cells by targeting ELOVL6/ACSL4, providing a new mechanism support for apatinib application in the clinical treatment of CRC.

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Section: Discussionmentioning

confidence: 99%

Apatinib Promotes Ferroptosis in Colorectal Cancer Cells by Targeting ELOVL6/ACSL4 Signaling

Tian

Li²,

Ge³

2021

CMAR

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The Effect of Silencing Fatty Acid Elongase 4 and 6 Genes on the Proliferation and Migration of Colorectal Cancer Cells

Czumaj,

Kobiela,

Mika

et al. 2023

IJMS

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Colorectal cancer (CRC) cells show some alterations in lipid metabolism, including an increased fatty acid elongation. This study was focused on investigating the effect of a small interfering RNA (siRNA)-mediated decrease in fatty acid elongation on CRC cells’ survival and migration. In our study, the elongase 4 (ELOVL4) and elongase 6 (ELOVL6) genes were observed to be highly overexpressed in both the CRC tissue obtained from patients and the CRC cells cultured in vitro (HT-29 and WiDr cell lines). The use of the siRNAs for ELOVL4 and ELOVL6 reduced cancer cell proliferation and migration rates. These findings indicate that the altered elongation process decreased the survival of CRC cells, and in the future, fatty acid elongases can be potentially good targets in novel CRC therapy.

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The effect of ELOVL6 fatty acid elongase inhibition on the expression of genes associated with the metastasis of breast cancer

Cited by 2 publications

References 70 publications

Apatinib Promotes Ferroptosis in Colorectal Cancer Cells by Targeting ELOVL6/ACSL4 Signaling

Apatinib Promotes Ferroptosis in Colorectal Cancer Cells by Targeting ELOVL6/ACSL4 Signaling

The Effect of Silencing Fatty Acid Elongase 4 and 6 Genes on the Proliferation and Migration of Colorectal Cancer Cells

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