Translational cancer research · 2026
Selenium metabolism-related gene TXNRD1 drives tumor progression and microenvironment remodeling in oral squamous cell carcinoma.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zhan Jun, Sun Qixiang, Zhu Wenyuan, Lu Xiao, He Yao
Аннотация
BACKGROUND: Selenium metabolism is implicated in redox regulation and tumor progression, yet its role in oral squamous cell carcinoma (OSCC) remains elusive. Thioredoxin reductase 1 (TXNRD1), a core selenoprotein, has been linked to malignant phenotypes, but its clinical relevance and biological functions in OSCC require further elucidation. Therefore, this study aimed to systematically investigate the prognostic value and biological functions of TXNRD1 in OSCC through multi-omics analysis and experimental validation.
METHODS: We integrated multi-omics data from The Cancer Genome Atlas (TCGA) and Molecular Signatures Database (MSigDB) to systematically screen selenium metabolism-related prognostic genes. Least absolute shrinkage and selection operator (LASSO) regression, single-cell transcriptomics GSE103322, and immune infiltration analyses were applied to evaluate the clinical value and microenvironmental features of TXNRD1. Furthermore, we established stable TXNRD1-knockdown OSCC cell lines HSC-2 using lentiviral-mediated short hairpin RNA (shRNA), and performed Cell Counting Kit-8 (CCK-8) proliferation assays, colony formation assays, and flow cytometry to validate its functional roles in vitro.
RESULTS: TXNRD1 was identified as a key selenium-related risk gene. It was significantly overexpressed in OSCC tissues and strongly correlated with poor overall survival area under the curve [area under the curve (AUC) =0.750]. Functional enrichment and single-cell analyses revealed that TXNRD1-high cancer cells were enriched in cell-cycle pathways (E2F targets, G2M checkpoint) and exhibited enhanced intercellular communication via MIF, LAMININ, and SPP1 pathways, along with associations with immune checkpoint genes PDCD1 and LAG3. Critically, our in vitro experiments demonstrated that TXNRD1 knockdown significantly suppressed OSCC cell viability and colony formation. Flow cytometric analysis further showed that TXNRD1 depletion induced a marked S-phase cell cycle arrest and significantly promoted apoptosis. Moreover, molecular docking predicted GSK591 as a potential compound targeting TXNRD1.
CONCLUSIONS: TXNRD1 drives OSCC progression through a dual mechanism-facilitating S-phase progression and suppressing apoptosis-and represents a promising prognostic biomarker and therapeutic target in OSCC.
METHODS: We integrated multi-omics data from The Cancer Genome Atlas (TCGA) and Molecular Signatures Database (MSigDB) to systematically screen selenium metabolism-related prognostic genes. Least absolute shrinkage and selection operator (LASSO) regression, single-cell transcriptomics GSE103322, and immune infiltration analyses were applied to evaluate the clinical value and microenvironmental features of TXNRD1. Furthermore, we established stable TXNRD1-knockdown OSCC cell lines HSC-2 using lentiviral-mediated short hairpin RNA (shRNA), and performed Cell Counting Kit-8 (CCK-8) proliferation assays, colony formation assays, and flow cytometry to validate its functional roles in vitro.
RESULTS: TXNRD1 was identified as a key selenium-related risk gene. It was significantly overexpressed in OSCC tissues and strongly correlated with poor overall survival area under the curve [area under the curve (AUC) =0.750]. Functional enrichment and single-cell analyses revealed that TXNRD1-high cancer cells were enriched in cell-cycle pathways (E2F targets, G2M checkpoint) and exhibited enhanced intercellular communication via MIF, LAMININ, and SPP1 pathways, along with associations with immune checkpoint genes PDCD1 and LAG3. Critically, our in vitro experiments demonstrated that TXNRD1 knockdown significantly suppressed OSCC cell viability and colony formation. Flow cytometric analysis further showed that TXNRD1 depletion induced a marked S-phase cell cycle arrest and significantly promoted apoptosis. Moreover, molecular docking predicted GSK591 as a potential compound targeting TXNRD1.
CONCLUSIONS: TXNRD1 drives OSCC progression through a dual mechanism-facilitating S-phase progression and suppressing apoptosis-and represents a promising prognostic biomarker and therapeutic target in OSCC.