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Inhibition of DDX60 Expression Suppresses Oral Squamous Cell Carcinoma Growth and Enhances Radiosensitivity
Vol 38, Issue 3, 2024
Abstract
Purpose: DEXD/H box helicase 60 (DDX60) overexpression in oral squamous cell carcinoma (OSCC) specimens has been reported extensively. Nevertheless, the radiosensitization implications of high-level DDX60 expression in OSCC remain unknown. This study aimed to investigate the biological function of DDX60 and confirm whether the inhibition of DDX60 could enhance radiosensitivity. Methods: DDX60 expression was measured by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis. After combination treatment of irradiation with or without DDX60-siRNA (small interfering RNA), the cell malignant behavior was determined using cell counting kit-8 (CCK-8) assay, flow cytometry, and transwell assays. The HSC6 xenograft models were utilized to measure the in vivo effects of combined treatment. Results: DDX60 was overexpressed in OSCC tissues and cells (p < 0.01, p < 0.05). HSC6 and SAS cells were transformed with DDX60-siRNA plasmids specifically reduced DDX60 gene expressions (p < 0.001, p < 0.01). DDX60 silencing notably hindered the proliferation and invasive abilities, and accelerated the apoptosis process (p < 0.01, p < 0.05). Suppression of DDX60 could enhance the 4 Gy irradiation-induced inhibiting in OSCC cell proliferation and invasion in HSC6 and SAS cells (p < 0.01, p < 0.05). Furthermore, the inhibition of DDX60 could promote the 4 Gy irradiation-induced apoptosis in HSC6 and SAS cells (p < 0.01, p < 0.05). Suppression of DDX60 also inhibited tumor growth in the HSC6 xenograft model (p < 0.01). Conclusions: The inhibition of DDX60 expression can promote radiosensitizing activity in human OSCC. Our results reveal that a multimodal therapy involving DDX60 expression inhibitors might be an effective radiosensitizer strategy in OSCC.
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Copyright (c) 2024 Hongxu Tian, Zhenying He, Ying Sun, Furong Zhao, Yun Wang, Lei Guo
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Medical Genetics, University of Torino Medical School, Italy

Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy