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. 2019 Mar;10(3):428-436.
doi: 10.1111/1759-7714.12944. Epub 2019 Feb 7.

Squalene epoxidase promotes the proliferation and metastasis of lung squamous cell carcinoma cells though extracellular signal-regulated kinase signaling

Hong Ge  1 , Yamei Zhao  2 , Xinyan Shi  1 , Zhen Tan  3 , Xiaorui Chi  1 , Man He  1 , Guohui Jiang  4 , Lixia Ji  4 , Hongmei Li  1
Affiliations

Squalene epoxidase promotes the proliferation and metastasis of lung squamous cell carcinoma cells though extracellular signal-regulated kinase signaling

Hong Ge et al. Thorac Cancer. 2019 Mar.

Abstract

Background: The biological function of squalene epoxidase (SQLE), an important rate-limiting enzyme in downstream cholesterol synthesis, is to convert squalene to 2-3 oxacin squalene. The expression of SQLE in lung cancer is abnormal. We conducted this study to investigate the effect of SQLE expression on lung squamous cell carcinoma (SCC) proliferation, migration, and invasion and its role in extracellular signal-regulated kinase (ERK) signaling.

Methods: Cell Counting Kit 8, wound healing, and Transwell assays; Western blotting; and quantitative real-time PCR were used to investigate the effect of SQLE in a lung SCC H520 cell line. Kaplan-Meier analysis was used to identify the prognostic significance of SQLE.

Results: Overexpression of SQLE promoted lung SCC cell proliferation, migration and invasion, whereas knockdown of SQLE expression showed the opposite effect. SQLE can interact with ERK to enhance its phosphorylation. SQLE may contribute to the pathogenesis of lung cancer by modulating ERK signaling. Further survival analysis indicated that high expression of SQLE indicated poor prognosis in lung SCC.

Conclusion: Our study presents novel evidence of potential biomarkers or therapeutic targets for lung SCC therapy and prognosis.

Keywords: ERK signal; SQLE; invasion; migration; proliferation.

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Figures

Figure 1
Figure 1
Squalene epoxidase (SQLE) expression levels in pancreatic ductal adenocarcinoma (a), prostate adenocarcinoma (b), hepatocellular carcinoma (c), lung SCC (d), breast carcinoma (e) based on data from the ONCOMINE database.
Figure 2
Figure 2
Squalene epoxidase (SQLE) overexpression promoted proliferation, migration, and invasion of lung squamous cell carcinoma (SCC) H520 cells. SQLE overexpression was verified by (a) quantitative real time‐PCR and (b,c) Western blotting. (d) Lung cancer cell proliferation was assayed using Cell Counting Kit 8. formula image Negative control (NC); formula image CON083; formula image SQLE. (e) Cell migration was detected by wound healing assay. (f) Cell invasion was detected by transwell assay. Each assay was repeated at least three times. Data from one representative experiment is presented as mean ± standard deviation. **, P < 0.01. GAPDH, glyceraldehyde 3‐phosphate dehydrogenase; mRNA, messenger RNA; OD, optical density.
Figure 3
Figure 3
Inhibition of squalene epoxidase (SQLE) expression reduced proliferation, migration, and invasion in lung squamous cell carcinoma (SCC) H520 cells and was verified by (a) quantitative real time‐PCR and (b,c) Western blotting. (d) Lung cancer cell proliferation was assayed using Cell Counting Kit 8. Negative control (NC)formula image; formula imageSQLE‐1853; formula image SQLE‐1640. (e) Cell migration was detected by wound healing assay. (f) Cell invasion was detected by transwell assay. Each assay was repeated at least three times. Data from one representative experiment is presented as mean ± standard deviation. **, P < 0.01 ***, P < 0.001. GAPDH, glyceraldehyde 3‐phosphate dehydrogenase; mRNA, messenger RNA; OD, optical density.
Figure 4
Figure 4
Alteration of squalene epoxidase (SQLE) expression regulated extracellular signal‐regulated kinase (ERK) phosphorylation levels. (a,b) Overexpression of SQLE stimulated the phosphorylation of ERK in lung squamous cell carcinoma (SCC) H520 cells. (c,d) SQLE knockdown inhibited ERK phosphorylation in lung SCC H520 cells. **, P < 0.01. GAPDH, glyceraldehyde 3‐phosphate dehydrogenase.
Figure 5
Figure 5
Kaplan–Meier plots for squalene epoxidase (SQLE) in lung squamous cell carcinoma (SCC). formula image low; formula image high. HR, hazard ratio.
See this image and copyright information in PMC

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