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

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

Ge H ，Zhao Y ，Shi X ，Tan Z ，Chi X ，He M ，Jiang G ，Ji L ，Li H ... -  《-》

Squalene epoxidase (SQLE) promotes the growth and migration of the hepatocellular carcinoma cells.

Sui Z ，Zhou J ，Cheng Z ，Lu P ... -  《-》

SQLE induces epithelial-to-mesenchymal transition by regulating of miR-133b in esophageal squamous cell carcinoma.

Increasing evidence suggests that microRNAs, which control gene expression at the post-transcriptional level, are aberrantly expressed in cancers and play significant roles in carcinogenesis and cancer progression. In this study, we show differential miR-133b down-expression in human esophageal squamous cell carcinoma (ESCC) cells and tissues. In addition, squalene epoxidase (SQLE), a key enzyme of cholesterol synthesis, is identified as the direct downstream target gene of miR-133b by luciferase gene reporter assay. Furthermore, ectogenic miR-133b expression and SQLE knockdown can inhibit proliferation, invasion, and metastasis, and diminish epithelial-to-mesenchymal transition (EMT) traits of ESCC in vitro, implying that miR-133b-dependent SQLE can induce tumorigenicity and that SQLE is an EMT inducer. Xenograft experiment results also proved the biological function of SQLE in vivo. Therefore, we conclude that miR-133b-dependent SQLE plays a critical role in the potential metastasis mechanisms in ESCC.

Qin Y ，Zhang Y ，Tang Q ，Jin L ，Chen Y ... -  《-》

Squalene epoxidase promotes breast cancer progression by regulating CCNB1 protein stability.

Tuluhong D ，Gao H ，Li X ，Wang L ，Zhu Y ，Xu C ，Wang J ，Li H ，Li Q ，Wang S ... -  《-》

SQLE-a promising prognostic biomarker in cervical cancer: implications for tumor malignant behavior, cholesterol synthesis, epithelial-mesenchymal transition, and immune infiltration.

Cervical cancer, encompassing squamous cell carcinoma and endocervical adenocarcinoma (CESC), presents a considerable risk to the well-being of women. Recent studies have reported that squalene epoxidase (SQLE) is overexpressed in several cancers, which contributes to cancer development. RNA sequencing data for SQLE were obtained from The Cancer Genome Atlas. In vitro experiments, including colorimetry, colony formation, Transwell, RT-qPCR, and Western blotting were performed. Furthermore, a transplanted CESC nude mouse model was constructed to validate the tumorigenic activity of SQLE in vivo. Associations among the SQLE expression profiles, differentially expressed genes (DEGs), immune infiltration, and chemosensitivity were examined. The prognostic value of genetic changes and DNA methylation in SQLE were also assessed. SQLE mRNA expression was significantly increased in CESC. ROC analysis revealed the strong diagnostic ability of SQLE toward CESC. Patients with high SQLE expression experienced shorter overall survival. The promotional effects of SQLE on cancer cell proliferation, metastasis, cholesterol synthesis, and EMT were emphasized. DEGs functional enrichment analysis revealed the signaling pathways and biological processes. Notably, a connection existed between the SQLE expression and the presence of immune cells as well as the activation of immune checkpoints. Increased SQLE expressions exhibited increased chemotherapeutic responses. SQLE methylation status was significantly associated with CESC prognosis. SQLE significantly affects CESC prognosis, malignant behavior, cholesterol synthesis, EMT, and immune infiltration; thereby offering diagnostic and indicator roles in CESC. Thus, SQLE can be a novel therapeutic target in CESC treatment.

Zhao YC ，Li YF ，Qiu L ，Jin SZ ，Shen YN ，Zhang CH ，Cui J ，Wang TJ ... -  《BMC CANCER》