Effects Of Squalene Epoxidase On Malignant Behavior And ERK Signaling Pathway In Lung Squamous Cell Carcinoma

Objective:The development and progression of lung squamous cell carcinoma(SCC)is extremely complicated.The effective treatment options are still relatively limited for patients with advanced lung SCC.With the advances of bioinformatics and gene detection technologies,research of tumor therapeutic targets has made breakthrough progress in the past decade.Metabolic changes,one of the most important features of cancer,and cancer development display mutual causality.And cholesterol metabolism alteration is one of the important metabolic alterations.Squalene epoxidase(SQLE)is one of the key enzymes on the downstream of the cholesterol synthesis pathway.This study was to investigate the effect and mechanism of SQLE on the growth,migration and invasion of lung SCC and explore the the role of SQLE in the prognosis of lung SCC.Methods: The expression of SQLE in lung SCC and normal lung tissue was analyzed by ONCOMINE database.The small interfering RNA and SQLE overexpression plasmid were used to regulate the expression level of SQLE gene in lung SCC H520 cell line,and the lung SCC cells with silenced and overexpressed SQLE was obtained.Then,the transcription and protein expression of the SQLE gene were verified by quantitative real-time PCR and Western blotting.The effects of silencing and overexpression SQLE gene on proliferation,migration and invasion of lung SCC cells were detected by Cell Counting Kit-8 test,wound healing test and Transwell test.Using Western blot to explore the role of SQLE gene in ERK signaling pathway.Patients with lung SCC in The Cancer Genome Altas database were screened and divided into high SQLE expression group and low SQLE expression group according to the expression level of SQLE.The relationship between the expression of SQLE and the prognosis of patients with lung SCC were analyzed by Kaplan-Meier.Results:The results of ONCOMINE database analysis showed that the expression level of SQLE in lung squamous cell carcinoma was significantly higher than that in normal lung tissue,that suggesting it may be involved in the development of lung SCC.SQLE expression was verified by quantitative real-time PCR and Western blotting.Overexpression of SQLE promoted lung SCC H520 cell proliferation,migration and invasion.Knockdown of SQLE suppressed the malignant behaviors of lung SCC H520 cell.The results of Western blotting showed that the expression of SQLE had a certain effect on ERK signaling pathway.Alteration of expression of SQLE could regulated ERK phosphorylation levels.Kaplan-Meier analysis showed that the expression of SQLE was obviously associated with the survival of lung SCC patients.The high expression of SQLE indicated poor survival prognosis of patients.Conclusion: The expression of SQLE in lung SCC is significantly higher than it’s in normal lung tissues.The expression of SQLE can promote the proliferation,migration and invasion of lung SCC.Alteration of expression of SQLE could regulated ERK phosphorylation levels.Combined with survival analysis,it can be concluded that SQLE is a biomarker for poor prognosis in patients with lung SCC.