HuD Promotes Progression of Oral Squamous Cell Carcinoma

Head and neck cancer, including oral squamous cell carcinoma (OSCC), ranks as the sixth most common malignancy worldwide. Overall 5-year survival rates of OSCC have not significantly improved during the past 3 decades and the 5-year survival rate is less than 50%. Several invasion grading systems have been employed in OSCC, however, their utility is still controversial. HuD belongs to the Hu protein family and acts as an RNA-binding protein involved in mRNA stability and translational regulation. Although HuD has a pivotal role for neuronal differentiation, the functional role of HuD in OSCCs is still unclear. In this study, we examined HuD expression in 82 OSCC cases. Expression of HuD was observed in 36.6% of OSCCs and significantly associated with histological differentiation, nodal metastasis and mode of invasion. HuD expression in high-metastatic HSC3 cells was higher than in low-metastatic HSC4 cells, and inhibition of invasion ability and activation of caspase-3 were shown by HuD siRNA-treated HSC3 cells. Furthermore, we clarified that HuD regulates expression of vascular endothelial growth factor (VEGF)-A, VEGF-D, matrix metallopeptidase (MMP)-2 and MMP-9. These results suggest that HuD is a useful diagnostic and therapeutic target in OSCCs. (C) 2014 S. Karger AG, Basel

头颈癌，包括口腔鳞状细胞癌（OSCC），在全球范围内是第六大常见恶性肿瘤。在过去的30年中，口腔鳞状细胞癌的总体5年生存率没有显著提高，5年生存率低于50%。在口腔鳞状细胞癌中已经应用了几种侵袭分级系统，然而，它们的实用性仍然存在争议。HuD属于Hu蛋白家族，作为一种RNA结合蛋白，参与mRNA的稳定性和翻译调控。尽管HuD在神经元分化中具有关键作用，但它在口腔鳞状细胞癌中的功能作用仍不清楚。在这项研究中，我们检测了82例口腔鳞状细胞癌病例中HuD的表达。在36.6%的口腔鳞状细胞癌中观察到HuD的表达，并且它与组织学分化、淋巴结转移和侵袭方式显著相关。在高转移性的HSC3细胞中HuD的表达高于低转移性的HSC4细胞，并且HuD siRNA处理的HSC3细胞显示出侵袭能力受到抑制以及caspase - 3被激活。此外，我们阐明了HuD调节血管内皮生长因子（VEGF）-A、VEGF - D、基质金属肽酶（MMP）-2和MMP - 9的表达。这些结果表明HuD是口腔鳞状细胞癌中一个有用的诊断和治疗靶点。（C）2014 S. Karger AG，巴塞尔