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》

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 ... -  《-》

A prognostic signature based on immune-related genes for cervical squamous cell carcinoma and endocervical adenocarcinoma.

Liu J ，Wu Z ，Wang Y ，Nie S ，Sun R ，Yang J ，Cheng W ... -  《-》

TPM3: a novel prognostic biomarker of cervical cancer that correlates with immune infiltration and promotes malignant behavior in vivo and in vitro.

Zhao YC ，Wang TJ ，Qu GH ，She LZ ，Cui J ，Zhang RF ，Qu HD ... -  《American Journal of Cancer Research》

SQLE, A Key Enzyme in Cholesterol Metabolism, Correlates With Tumor Immune Infiltration and Immunotherapy Outcome of Pancreatic Adenocarcinoma.

Pancreatic adenocarcinoma (PAAD) is a treatment-refractory cancer with poor prognosis. Accumulating evidence suggests that squalene epoxidase (SQLE) plays a pivotal role in the development and progression of several cancer types in humans. However, the function and underlying mechanism of SQLE in PAAD remain unclear. SQLE expression data were downloaded from The Cancer Genome Atlas and the Genotype-Tissue Expression database. SQLE alterations were demonstrated based on the cBioPortal database. The upstream miRNAs regulating SQLE expression were predicted using starBase. The function of miRNA was validated by Western blotting and cell proliferation assay. The relationship between SQLE expression and biomarkers of the tumor immune microenvironment (TME) was analyzed using the TIMER and TISIDB databases. The correlation between SQLE and immunotherapy outcomes was assessed using Tumor Immune Dysfunction and Exclusion. The log-rank test was performed to compare prognosis between the high and low SQLE groups. We demonstrated a potential oncogenic role of SQLE. SQLE expression was upregulated in PAAD, and it predicted poor disease-free survival (DFS) and overall survival (OS) in patients with PAAD. "Amplification" was the dominant type of SQLE alteration. In addition, this alteration was closely associated with the OS, disease-specific survival, DFS, and progression-free survival of patients with PAAD. Subsequently, hsa-miR-363-3p was recognized as a critical microRNA regulating SQLE expression and thereby influencing PAAD patient outcome. In vitro experiments suggested that miR-363-3p could knock down the expression of SQLE and inhibit the proliferation of PANC-1. SQLE was significantly associated with tumor immune cell infiltration, immune checkpoints (including PD-1 and CTLA-4), and biomarkers of the TME. KEGG and GO analyses indicated that cholesterol metabolism-associated RNA functions are implicated in the mechanisms of SQLE. SQLE was inversely associated with cytotoxic lymphocytes and predicted immunotherapy outcomes. Collectively, our results indicate that cholesterol metabolism-related overexpression of SQLE is strongly correlated with tumor immune infiltration and immunotherapy outcomes in patients with PAAD.

You W ，Ke J ，Chen Y ，Cai Z ，Huang ZP ，Hu P ，Wu X ... -  《Frontiers in Immunology》