Wang Xing, Bai Yuting, Han Ying, Meng Jian, Liu Hongwei
Department of Oral Medicine, Peking University School and Hospital of Stomatology, Beijing, People's Republic of China.
Department of Oromaxillofacial-Head and Neck Surgery, Affiliated Xuzhou Hospital, College of Medicine, Southeast University, Xuzhou, JiangSu, People's Republic of China.
Onco Targets Ther. 2019 May 17;12:3729-3742. doi: 10.2147/OTT.S207930. eCollection 2019.
Oral squamous cell carcinoma (OSCC) is the most common and severe type of head and neck malignancy. The mechanisms by which OSCC arises depend on changes in a number of different factors and genes and the clinicopathological stage of the tumors. Better understanding the possible mechanisms of OSCC would help to identify a new target for molecular targeted therapy. The current study was focused on elucidating the significance of the glioblastoma-amplified sequence (GBAS) on malignant behaviors in OSCC, including proliferation and apoptosis. In this study, we measured the levels of mRNA in OSCC and normal oral tissue samples using Affymetrix microarrays. We examined GBAS expression in OSCC tissues and the effect of GBAS knockdown on cell proliferation and apoptosis in vitro and in vivo. The mechanisms underlying GBAS were investigated. In the present study, GBAS expression was substantially elevated in the majority of tested OSCC tissues. Further, knockdown of GBAS using lentiviral-delivered shRNA in cells had significant effects on cell proliferation, apoptosis and the cell cycle. A xenograft model was also used to assess the tumorigenicity of the GBAS knockdown on OSCC cells in vivo. Mechanistically, GBAS activated p53 signaling by regulating the mRNA and protein expression of CHEK1, AKT1, AKT2 and Bax. Finally, we also investigated the expression of GBAS in patients with OSCC, and the data revealed that GBAS expression was correlated with the rates of relapse and tumor grade. Our studies provide evidence that GBAS regulates OSCC cell proliferation and apoptosis via p53 signaling, which may be a candidate biomarker for the prognosis and treatment of OSCC.
口腔鳞状细胞癌（OSCC）是头颈部最常见且最严重的恶性肿瘤类型。OSCC发生的机制取决于多种不同因素、基因的变化以及肿瘤的临床病理分期。更好地了解OSCC可能的机制将有助于确定分子靶向治疗的新靶点。当前的研究聚焦于阐明胶质母细胞瘤扩增序列（GBAS）在OSCC恶性行为（包括增殖和凋亡）中的意义。在本研究中，我们使用Affymetrix微阵列测量了OSCC和正常口腔组织样本中的mRNA水平。我们检测了GBAS在OSCC组织中的表达以及GBAS敲低对体外和体内细胞增殖及凋亡的影响。对GBAS的潜在机制进行了研究。在本研究中，大多数测试的OSCC组织中GBAS表达显著升高。此外，在细胞中使用慢病毒递送的shRNA敲低GBAS对细胞增殖、凋亡和细胞周期有显著影响。还使用异种移植模型评估了GBAS敲低对体内OSCC细胞致瘤性的影响。从机制上讲，GBAS通过调节CHEK1、AKT1、AKT2和Bax的mRNA和蛋白质表达激活p53信号通路。最后，我们还研究了OSCC患者中GBAS的表达，数据显示GBAS表达与复发率和肿瘤分级相关。我们的研究提供了证据，表明GBAS通过p53信号通路调节OSCC细胞增殖和凋亡，这可能是OSCC预后和治疗的候选生物标志物。
