SQLE facilitates laryngeal squamous cell carcinoma progression via PI3K/AKT signaling-mediated dysregulation of lipid metabolism

Background: Squalene Monooxygenase (SQLE) is the second rate-limiting enzyme in cholesterol biosynthesis and plays a critical role in the cholesterol biosynthesis pathway. SQLE has recently been shown to play animportant role in human tumors. However,its role in laryngeal squamous cell carcinoma (LSCC) remains unclear. Methods: Single-cell sequencing (scRNA-seq), transcriptomicsequencing (RNA-seq) and proteomics were used to preliminarily determine that SQLE is significantly overexpressed in LSCC tissues. Immunohistochemical(IHC) and quantitative real-time PCR were used to investigate the expression of SQLE in tissue samples and cell lines. Western bloting was used to investigate the expression of SQLE 、PI3K and AKT in LSCC cell lines.The biological effects of SQLE were detected in vitro. A Phalloidin-TRITC staining assay was used to observe the effect of SQLE on the cytoskeleton morphology of LSCC cells.BODIPY staining assay was used to observe lipid droplet and Filipin staining assay was used to observe cholesterol expression after SQLEknocked down in LSCC cells. Results: SQLE was significantly increased in patients with LSCC and was associated with an unfavorable prognosis. The knockdown of SQLE reduced the proliferation, invasion and migration of LSCC cells. The expression of lipid droplet and cholesterol were reduced after SQLE was koncked down.These effects were reversed after treatment with the PI3K/AKT signaling agonist 740 Y-P. Conclusion: Our results reveal that SQLE functions as an oncogene that promotes LSCC growth by activating the lipid metabolism-regulated PI3K/AKT signaling pathway, highlighting the potential of SQLE as atherapeutic target for treating LSCC.