The circEPSTI1/mir-942-5p/LTBP2 axis regulates the progression of OSCC in the background of OSF via EMT and the PI3K/Akt/mTOR pathway
The circEPSTI1/mir-942-5p/LTBP2 axis regulates the progression of OSCC in the background of OSF via EMT and the PI3K/Akt/mTOR pathway
复制标题
circEPSTI1/mir-942-5p/LTBP2 轴通过 EMT 和 PI3K/Akt/mTOR 通路在 OSF 背景下调节 OSCC 的进展
DOI：
10.1038/s41419-020-02851-w
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发表时间：
2020-08-12
影响因子：
9
通讯作者：
He, Caiyun
中科院分区：
文献类型：
--
作者：
Wang, Jie;Jiang, Canhua;He, Caiyun
咀嚼槟榔引起的口腔黏膜下纤维化（OSF）背景下的口腔鳞状细胞癌（OSCC）在亚太国家发病率较高。然而，分子机制尚不清楚。在这里，我们进行了circRNA微阵列分析，以筛选OSCC和OSF中的circRNA表达谱。我们发现circEPSTI1是一个circRNA，从正常颊黏膜（NBM）到OSF再到OSCC都有一致的、顺序的上调。功能上，circEPSTI1显著促进了OSCC细胞的增殖和侵袭，CCK8、菌落形成、伤口愈合以及circEPSTI1过表达和沉默的transwell实验证明了这一点。伴有circepsti1高状态的OSCC患者预后较差。CircEPSTI1通过磷酸化PI3K/Akt/mTOR信号通路组分，海绵化miR-942-5p，加速上皮-间质转化（EMT），增加OSCC中LTBP2的表达。用双PI3K/ mTOR抑制剂BEZ235阻断PI3K/Akt/mTOR信号通路，可逆转circEPSTI1和LTBP2过表达诱导的OSCC进展。综上所述，这些结果表明circEPSTI1/miR-942-5p/LTBP2轴通过加速EMT和PI3K/Akt/mTOR信号通路组分的磷酸化影响OSCC细胞的增殖和侵袭。CircEPSTI1可能是OSCC合并OSF患者的独立诊断和预后标志物，也是潜在的治疗靶点。
Oral squamous cell carcinoma (OSCC) in the background of oral submucous fibrosis (OSF) caused by areca nut chewing has a high incidence in Asia-Pacific countries. However, the molecular mechanism remains unclear. Here, we performed circRNA microarray analysis to screen the circRNA expression profiles in OSCC and OSF. We identified circEPSTI1 as a circRNA with consistent, sequential upregulation from normal buccal mucosa (NBM) to OSF to OSCC. Functionally, circEPSTI1 significantly promoted OSCC cell proliferation and invasion, as evidenced by the CCK8, colony formation, wound healing, and transwell assays with circEPSTI1 overexpression and silencing. OSCC patients with circEPSTI1highstatus exhibited poor prognoses. CircEPSTI1 sponged miR-942-5p and accelerated epithelial-mesenchymal transition (EMT) to increase LTBP2 expression in OSCC through phosphorylation of PI3K/Akt/mTOR signaling pathway components. Blocking the PI3K/Akt/mTOR signaling pathway with the dual PI3k/mTOR inhibitor BEZ235 reversed OSCC progression induced by overexpression of circEPSTI1 and LTBP2. Collectively, these results indicate that the circEPSTI1/miR-942-5p/LTBP2 axis affects OSCC cell proliferation and invasion via the acceleration of EMT and the phosphorylation of PI3K/Akt/mTOR signaling pathway components. CircEPSTI1 may be an independent diagnostic and prognostic marker and a potential therapeutic target for OSCC patients with OSF.