Identification of activating transcription factor 6 (ATF6) as a novel prognostic biomarker and potential target in oral squamous cell carcinoma

Abstract

Background: 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.

Methods: 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. RESULTS: Bioinformatics analyses showed that ATF6 overexpression was associated with prognosis and detrimental to survival. In vitro studies verified that ATF6 knockdown reduced OSCC cell proliferation and migration. Mechanistically, ATF6 knockdown could promote cellular autophagy and apoptosis.

Conclusion: 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.

Keywords: Activating transcription factor 6 (ATF6); Autophagy; Biomarker; Oral squamous cell carcinoma (OSCC); Prognosis; Targeted therapy.