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Cell proliferation of oral squamous cell carcinoma (OSCC) is precisely regulated with a cascade of genes and pathways. Previous studies have identified NR4A1 as an oncogene and plays a crucial role in colorectal cancer development and progression. This study was performed to investigate the potential interaction between lncRNA NR4A1AS and miR-221 and how their interaction is modulated in periodontitis. Research subjects of this study included 62 OSCC patients. Cell transfection and RT-qPCR were applied to detect the expression levels of