lncRNA-FAM225A在鼻咽癌转移中的作用和分子机制研究

远处转移是鼻咽癌治疗失败的主要原因（占70%），使用现行的TNM临床分期来预测远处转移的准确性仅63.6%。如何结合分子指标筛选出高转移风险的病例，并予以个体化治疗，是降低远处转移面临的挑战。lncRNA被证实在肿瘤转移中起着重要作用。我们的前期研究提示：①采用lncRNA芯片能够筛选出在鼻咽癌组织和细胞中均显著高表达的lncRNA-FAM225A；定量PCR也验证了该结果；②迁移和侵袭实验提示敲减lncRNA-FAM225A后可抑制鼻咽癌细胞的迁移和侵袭能力，但具体作用机制不明；③小样本生存分析发现，lncRNA-FAM225A表达水平高的鼻咽癌患者，无远处转移生存和总生存均较差。本课题拟在上述基础上：①阐明lncRNA-FAM225A在鼻咽癌远处转移中的具体作用及分子机制；②在大样本中验证lncRNA-FAM225A对远处转移的预测价值，为鼻咽癌的“个体化”治疗提供新的靶点和分子指标。

In nasopharyngeal carcinoma (NPC), about 70% of the treatment failures are ascribed to distant metastasis. The accuracy of current clinical TNM staging system to predict distant metastasis is only 63.6%. How to integrate molecular indicators with clinical TNM staging system to screen out patients with high risk of metastasis and guide individualized therapy is a challenge to reduce distant metastasis. To date, long noncoding RNAs (lncRNAs) has been proved to play important roles in tumor metastasis. Our preliminary studies revealed that ① lncRNA-FAM225A was significantly upregulated in NPC tissue samples and cell lines, which was also validated by quantitative PCR; ② migration and invasion assays suggest that knockdown of lncRNA-FAM225A inhibited the migration and invasion of NPC cells, however, the mechanism remains unknown; ③ survival analysis indicted that patients with high level of lncRNA-FAM225A expression suffered poor distant metastasis-free survival and overall survival. In this project, we will ① elucidate the function and molecular mechanism of lncRNA-FAM225A in NPC metastasis; ② validate the predictive value of lncRNA-FAM225A in NPC metastasis. This research will provide a potential novel target and molecular indicators for individual therapy of NPC patients.