Oral squamous cell carcinoma (OSCC) is originating from oral mucosal epithelial cells. Autophagy plays a crucial role in cancer treatment by promoting cellular self-degradation and eliminating damaged components, thereby enhancing therapeutic efficacy. In this study, we aim to identify a novel autophagy-related biomarker to improve OSCC therapy. We firstly utilized Cox and Lasso analyses to identify that ATF6 is associated with OSCC prognosis, and validated the results by Kaplan-Meier survival analysis. We further identified the downstream pathways and related genes by enrichment analysis and WGCNA analysis. Subsequently, we used short interfering RNA to investigate the effects of ATF6 knockdown on proliferation, migration, apoptosis, and autophagy in SCC-9 and SCC-15 cells through cell viability assay, transwell assay, EdU incorporation assay, flow cytometry analysis, western blot analysis and immunofluorescence analysis, etc. Bioinformatics analyses showed that ATF6 overexpression was associated with prognosis and detrimental to survival. studies verified that ATF6 knockdown reduced OSCC cell proliferation and migration. Mechanistically, ATF6 knockdown could promote cellular autophagy and apoptosis. We propose that ATF6 holds potential as a prognostic biomarker linked to autophagy in OSCC. This study provides valuable clues for further exploration of targeted therapy against OSCC.

中文翻译：

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鉴定激活转录因子 6 (ATF6) 作为口腔鳞状细胞癌的新型预后生物标志物和潜在靶标

口腔鳞状细胞癌（OSCC）起源于口腔粘膜上皮细胞。自噬在癌症治疗中发挥着至关重要的作用，它可以促进细胞自我降解并消除受损成分，从而提高治疗效果。在这项研究中，我们的目标是确定一种新型的自噬相关生物标志物来改善口腔鳞癌的治疗。我们首先利用 Cox 和 Lasso 分析确定 ATF6 与 OSCC 预后相关，并通过 Kaplan-Meier 生存分析验证结果。我们通过富集分析和WGCNA分析进一步鉴定了下游通路和相关基因。随后，我们使用短干扰RNA，通过细胞活力测定、transwell实验、EdU掺入实验、流式细胞术分析、蛋白质印迹研究ATF6敲低对SCC-9和SCC-15细胞增殖、迁移、凋亡和自噬的影响。生物信息学分析表明ATF6过表达与预后相关，不利于生存。研究证实，ATF6 敲除可减少 OSCC 细胞的增殖和迁移。从机制上讲，ATF6 敲低可以促进细胞自噬和凋亡。我们认为 ATF6 具有作为 OSCC 中与自噬相关的预后生物标志物的潜力。该研究为进一步探索口腔鳞癌的靶向治疗提供了有价值的线索。