Liu Jin, Yang Qiaozhen, Sun Hongying, Wang Xiaxia, Saiyin Hexige, Zhang Hui
Department of Stomatology, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.
State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, People's Republic of China.
Cancer Manag Res. 2020 Aug 12;12:7219-7230. doi: 10.2147/CMAR.S251348. eCollection 2020.
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.
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.
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 (<0.05). When ENO1 was knocked down in cal-27, cell proliferation was inhibited (<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.
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.
口腔鳞状细胞癌（OSCC）可能由多种口腔潜在恶性疾病发展而来，但其恶性转化机制仍不清楚。其中，口腔扁平苔藓（OLP）患病率较高。既往研究表明，α-烯醇化酶（ENO1）可促进细胞增殖，在肿瘤发生中起重要作用。在本研究中，我们旨在探讨OLP向OSCC肿瘤发生过程中ENO1调控的机制。
采用实时定量PCR和免疫组织化学检测组织中ENO1表达。在cal-27细胞中敲低ENO1以观察细胞增殖变化。然后，对OLP和OSCC样本进行RNA测序和生物信息学分析。使用实时定量PCR评估circ-AMOTL1、miRNA-22-3p和miRNA-1294的表达。在体外敲低和过表达circ-AMOTL1后，还评估了ENO1在mRNA水平的变化。
与OLP相比，OSCC样本中ENO1表达增强。免疫组织化学和实时定量PCR结果显示，OSCC组织中ENO1明显高于OLP组，差异有统计学意义（<0.05）。当在cal-27细胞中敲低ENO1时，细胞增殖受到抑制（<0.05）。OSCC组织中miR-22-3p和miR-1294表达降低，而ENO1和circ-AMOTL1升高。在体外研究中，敲低circ-AMOTL1导致ENO1降低，而过表达circ-AMOTL1导致ENO1在mRNA水平升高。
我们证实OSCC中ENO1表达升高并增加细胞增殖。在体外研究中，circ-AMOTL1促进ENO1表达。ENO1可能通过circ-AMOTL1/miR-22-3p/miR-1294网络在OSCC中作为促癌基因发挥作用。这些新发现可能进一步阐明从OLP到OSCC的发病机制及潜在的前驱标志物。
