Cancer Management and Research (Aug 2020)
The circ-AMOTL1/ENO1 Axis Implicated in the Tumorigenesis of OLP-Associated Oral Squamous Cell Carcinoma
Abstract
Jin Liu,1,* Qiaozhen Yang,1,* Hongying Sun,1 Xiaxia Wang,1 Hexige Saiyin,2 Hui Zhang1 1Department of Stomatology, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 2State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongying Sun Tel +86-21-52887810Email [email protected]: Oral squamous cell carcinoma (OSCC) may develop from a variety of oral potentially malignant disorders, but the mechanism of malignant transformation is still unknown. Among them, oral lichen planus (OLP) has a high prevalence. Previous studies have shown that α-enolase (ENO1) can promote cell proliferation and play an important role in tumorigenesis. In this study, we aim to explore the mechanism of ENO1 regulation in the process of OSCC tumorigenesis from OLP.Methods: ENO1 expression in tissues was determined by real-time quantitative PCR and immunohistochemistry. ENO1 was knocked down in cal-27 to observe the change in cell proliferation. Then, RNA-seq and bioinformatics analyses were conducted between OLP and OSCC samples. The expression of circ-AMOTL1, miRNA-22-3p, and miRNA-1294 was assessed using the real-time quantitative PCR. With knockdown and overexpression of circ-AMOTL1 in vitro, the change of ENO1 in the mRNA level was also assessed.Results: ENO1 was enhanced in the OSCC samples in comparison with OLP. Immunohistochemistry and real-time quantitative PCR results showed that ENO1 was significantly higher in OSCC tissue than in the OLP group, with a statistically significant difference (p< 0.05). When ENO1 was knocked down in cal-27, cell proliferation was inhibited (p< 0.05). The expression of miR-22-3p and miR-1294 was decreased in OSCC tissues, whereas ENO1 and circ-AMOTL1 increased. In an in vitro study, knockdown of circ-AMOTL1 resulted in a decrease of ENO1, while overexpression of circ-AMOTL1 led to an increase of ENO1 in the mRNA level.Conclusion: We confirmed that ENO1 expression was elevated in OSCC and increased cell proliferation. In an in vitro study, ENO1 expression was promoted by circ-AMOTL1. ENO1 may play a role as a tumor-promoting gene in OSCC through the circ-AMOTL1/miR-22-3p/miR-1294 network. These novel findings may shed further light on the pathogenesis from OLP to OSCC and the potential precursor markers.Keywords: oral lichen planus, oral squamous cell carcinoma, ENO1, AMOTL1, ceRNA
