lncRNA NR4A1AS Upregulates miR-221 Through Demethylation to Promote Cell Proliferation in Oral Squamous Cell Carcinoma

BACKGROUND: 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. PATIENTS AND METHODS: Research subjects of this study included 62 OSCC patients. Cell transfection and RT-qPCR were applied to detect the expression levels of NR4A1AS and miR-221. Methylation-specific PCR (MSP) was carried out to determine the demethylation of miR-221 by NR4A1AS. CCK-8 assay was used to detect the proliferation of OSCC cells with the overexpression of NR4A1AS or/and overexpression of miR-221. RESULTS: In this study, we observed that NR4A1AS was upregulated in tumor tissue samples of OSCC, and its high expression levels were significantly correlated with poor survival in patients with OSCC. In addition, miR-221 was significantly down-regulated in OSCC tumors. NR4A1AS and miR-221 were significantly and positively correlated in OSCC tumors but not in non-dysplastic tissue. In OSCC cells, overexpression of NR4A1AS led to upregulation of miR-221 and decreased the methylation of miR-221 gene. However, overexpression of miR-221 did not affect the expression of NR4A1AS in OSCC cells. In addition, overexpression of NR4A1AS or miR-221 increased the proliferation rate of OSCC cells. CONCLUSION: This study is the first to report that NR4A1AS is upregulated in OSCC. Moreover, we also propose that miR-221 is modulated by NR4A1AS through demethylation and the upregulation of NR4A1AS or miR-221 promotes the proliferation of OSCC cells, which suggests that anti-NR4A1AS might be a perspective approach for the therapy of OSCC.