MicroRNA-324-5p介导甲状腺乳头状癌淋巴结转移的应用基础研究

寻找有效预测甲状腺乳头状癌（PTC）相关淋巴结转移（LNM）的标记物及发生机理对疾病治疗和预后具有重要临床意义。课题组前期基于LNM阳性和阴性的PTC组织标本miRNAs表达谱分析鉴定，发现miR-324-5p在LNM阳性组中异常上调，有望成为其分子标记物。但miR-324-5p在PTC-LNM中异常上调的原因仍不明确。通过UCSC数据库转录活性区域预测，基因miR-324的上游存在两处转录信号的富集区域。因此我们将从转录调控入手，明确目标基因的启动子和上游转录因子；观察转录因子含量是否发生改变；阐明异常调控通过改变肿瘤微环境促进PTC肿瘤细胞的侵袭和迁移能力的机制。在此基础上，通过临床大样本检测，进一步证实miR-324-5p的表达调控水平与PTC患者临床转归的关系。最终明确PTC患者发生LNM的机制，并为PTC-LNM的早期发现及治疗提供潜在新靶点。

Lymph node metastasis (LNM) is a pivotal risk factor of papillary thyroid carcinoma (PTC), which influences the management and prognosis. Based on the genome-wide miRNAs expression profile analysis and identification, miR-324-5p was found to be significantly overexpressed in tissue samples of PTC with lymph node metastasis. Most LNM in unifocal intrathyroidal PTMC can be predicted by miR-324-5p detection in fine needle aspiration (FNA) lavage fluid, which made up for the deficiency of conventional ultrasound to some extent. However, the mechanism under the abnormal up-regulation of miR-324-5p in PTC-LNM is still obscure. Transcriptional activity regions retrieved from UCSC database indicated that there are two enrichment regions of upstream transcription signal of miR-324. Therefore, in this study, we intend to 1) identify the promoter and upstream transcription factors of miR-324-5p; 2) clarify how transcription factors regulate the target gene; 3) validate the hypothesis that abnormal up-regulation of miR-324-5p induces alteration in tumor microenvironment and facilitates migration/invasion of PTC cells; 4) verify the relationship between miR-324-5p and clinical outcome of PTC patients in larger scale tissue samples. Above all, our research aims to find out the mechanism of PTC related LNM, and offer potential target for early detection and management of PTC-LNM.