lncRNA调控淋巴管生成在口腔鳞癌颈淋巴转移中的作用及其机制

Oral squamous cell carcinoma(OSCC) is the most common malignant tumor in oral and maxillofacial region, regional metastasis of cervical lymph node occur frequently, even in early oral cancer. However, the mechanism of metastasis is still unclear until now, and there is no efficient method for early diagnosis. Lymphangiogenesis of tumor has been found having relation with the neck metastasis of OSCC recently, but the molecular regulation mechanism of lymphangiogenesis is unknown. The current researches show long non-coding RNA(lncRNA) deeply involve in tumor invasion and metastasis of many human cancer. Until now, there is no report of lncRNA regulation tumor metastasis and lymphangiogenesis in OSCC. In this project, the lncRNAs which associate with the metastasis of OSCC will be screened by microarray technique, the target genes will be identified, and finally find the lncRNAs which play important role in lymphangiogenesis and lymph node metastasis of OSCC. Then, in vitro, assess the effect of lncRNA on the regulation factor of lymphangiogenesis by cell experiment. Establishing the animal model of cervical lymph node metastasis of OSCC, in vivo, assess the function of lncRNA in lymphangiogenesis and metastasis of OSCC. By all the above, we try to find the functional lncRNA which play important role in tumor metastasis and lymphangiogenesis of OSCC. This study will help us understand the molecular mechanism of tumor lymphangiogenesis and cervical metastasis of OSCC, and will benefit the early diagnosis and treatment intervention of OSCC neck metastasis.

口腔鳞状细胞癌是口腔颌面部最多见的恶性肿瘤，常发生区域颈淋巴结转移，但转移机制迄今仍不明确，亦缺乏有效的早期诊断手段。近期研究发现口腔鳞癌淋巴管生成与颈淋巴转移密切相关，而肿瘤淋巴管生成调控的分子机制尚不清楚。新近研究表明lncRNA参与肿瘤侵袭转移过程中的基因表达调控。本课题拟通过lncRNA芯片技术筛选出和口腔鳞癌颈淋巴转移相关的lncRNA，明确其作用靶点，确定在调节淋巴管生成、淋巴结转移中起关键作用的lncRNA。通过体外实验在细胞水平检测功能性lncRNA对淋巴管生成关键因子表达的影响。再通过口腔鳞癌颈淋巴转移动物模型实验，观察功能性lncRNA在体内对口腔鳞癌淋巴管生成和颈淋巴转移的作用。由此确定与口腔鳞癌颈淋巴转移相关的功能性lncRNA，为探索口腔鳞癌颈淋巴转移的早期诊断和治疗干预的新途径奠定基础，同时进一步揭示肿瘤淋巴管生成和口腔鳞癌颈淋巴转移的分子机制。

口腔鳞状细胞癌是口腔颌面部常见的易发生区域性颈淋巴结转移恶性肿瘤。近期研究报道长链非编码RNA（lncRNA）参与肿瘤侵袭转移过程中的基因表达调控。本课题首先通过免疫组化研究，观察了口腔鳞癌瘤内及瘤周淋巴管生成情况，并联合肿瘤浸润深度等临床病理指标，分析其与肿瘤颈淋巴结转移的相关性。进一步通过lncRNA芯片技术筛选出了和口腔鳞癌颈淋巴结转移相关的lncRNA---NR_002819(MALAT1)和NR_002323 (TUG1)，并通过生物信息学分析探讨了它们在调节淋巴管生成、淋巴结转移中的作用，筛选出了可能与它们协同发挥作用的关键因子-- EWSR1、BTK、CAV1、Tp53等。为进一步研究口腔鳞癌颈淋巴结转移的早期诊断和治疗干预提供了新方向。