Stomatological Department of Guangdong Women and Children Hospital, Guangzhou City, Guangdong Province, 511400, PR China.
Functional Department of Baoding Second Central Hospital, Zhuozhou City, Hebei Province, 072750, PR China.
Arch Oral Biol. 2018 Dec;96:52-57. doi: 10.1016/j.archoralbio.2018.06.003. Epub 2018 Jun 6.
Our study aimed to investigate the functionality of miR-200c in oral squamous cell carcinoma.
Tumor tissues and adjacent tissues were obtained from oral squamous cell carcinoma patients, and blood samples were extracted from both oral squamous cell carcinoma patients and healthy controls. Expression of miR-200c in those tissues was detected by qRT-PCR. All patients were followed-up for 5 years and ROC curves as well as survival analyses were performed to evaluate the diagnostic as well as prognostic values of serum miR-200c for oral squamous cell carcinoma. miR-200c and Glut1 overexpression oral squamous cell carcinoma cell lines were constructed and cell proliferation was detected by CCK-8 assay. Glucose uptake was determined by glucose uptake assay. Interactions between miR-200c, Akt and Glut1 were explored by western blot.
Expression of miR-200c was significantly downregulated in tumor tissues comparing with adjacent tissues in most oral squamous cell carcinoma patients. Serum level of miR-200c was lower in oral squamous cell carcinoma patients than that in healthy controls, and it was decreased with increased primary tumor stages. Serum levels of miR-200c can been used to effectively distinguish oral squamous cell carcinoma patients from healthy control, and patients with lower serum level of miR-200c showed shorter survival time. miR-200c overexpression inactivated Akt and Glut1 expression, while Akt activator and Glut1 overexpression showed no significant effects on miR-200c. Akt activator promoted Glut1 expression, but Glut1 overexpression showed no significant effects on Akt. MiR-200c inhibited cell proliferation and glucose uptake, while Akt activator and Glut1 overexpression reduced the inhibitory effect of miR-200c overexpression on cell proliferation.
miR-200c can inhibit the proliferation of oral squamous cell carcinoma cells by targeting Akt pathway and its downstream Glut1.
本研究旨在探讨 miR-200c 在口腔鳞状细胞癌中的功能。
从口腔鳞状细胞癌患者中获取肿瘤组织和相邻组织，并从口腔鳞状细胞癌患者和健康对照者中提取血液样本。通过 qRT-PCR 检测这些组织中 miR-200c 的表达。对所有患者进行 5 年随访，并通过 ROC 曲线和生存分析评估血清 miR-200c 对口腔鳞状细胞癌的诊断和预后价值。构建 miR-200c 和 Glut1 过表达的口腔鳞状细胞癌细胞系，并通过 CCK-8 检测细胞增殖。通过葡萄糖摄取测定法测定葡萄糖摄取。通过 Western blot 探讨 miR-200c、Akt 和 Glut1 之间的相互作用。
在大多数口腔鳞状细胞癌患者中，肿瘤组织中 miR-200c 的表达明显低于相邻组织。与健康对照组相比，口腔鳞状细胞癌患者血清 miR-200c 水平较低，且随着原发肿瘤分期的增加而降低。血清 miR-200c 水平可有效区分口腔鳞状细胞癌患者与健康对照组，血清 miR-200c 水平较低的患者生存时间较短。miR-200c 过表达可使 Akt 和 Glut1 表达失活，而 Akt 激活剂和 Glut1 过表达对 miR-200c 无显著影响。Akt 激活剂促进 Glut1 表达，但 Glut1 过表达对 Akt 无显著影响。miR-200c 抑制细胞增殖和葡萄糖摄取，而 Akt 激活剂和 Glut1 过表达可降低 miR-200c 过表达对细胞增殖的抑制作用。
miR-200c 可通过靶向 Akt 通路及其下游 Glut1 抑制口腔鳞状细胞癌细胞的增殖。
