乳头状甲状腺癌（PTC）是最常见的甲状腺癌，部分会侵犯淋巴结，产生一系列严重的症状和体征。B-RAFV600E突变是PTC主要的遗传学特征,但PTC的发病机制仍不清楚。近期，脂代谢异常与肿瘤发生发展的关系受到关注。申请者对PTC的血清和组织代谢小分子谱的研究显示：PTC的脂肪酸β－氧化（该过程的限速酶为肉碱脂酰转移酶I，CPT1）加速(Mol.Biosystems, 2011)，而原本表达于脑部的CPT1C亚型在PTC组织中表达显著上调，课题组的结果还提示B-RAFV600E可上调CPT1C。本项目拟研究（1）PTC癌组织中CPT1C的上调对PTC的脂肪代谢和恶性表型起何作用，有何意义；（2）PTC癌组织中CPT1C异常升高的分子机制是什么？包括是否与B-RAF经由miR-370调节有关系？阐明以上问题，有助全面认识PTC的分子发病机制，有望为研发新的治疗手段提供有效靶标。

Papillary thyroid cancer (PTC), the most common type of thyroid carcinoma, has an impressive propensity for lymphatic spread. While it is well recognized that activating B-RAFV600E is the most prevalent mutation, understanding of the complete range of pathways involved in its pathogenesis is incomplete.Our earlier research, with metabonomics analysis （published in Mol Biosystmes ,2011） and clinical specimens check, found that fatty acid β-oxidation was promoted and brain type of carnitine palmitoyl-transferase 1 (CPT1) isozymes, CPT1C，was up-regulated. What is more, activating B-RAFV600E could induce CPT1C . In this project, we would like to confirm and partly clarify the significance of CPT1C up-regulation toward lipid metabolism and carcinogenesis under metabolic stress. Besides, it is to be confirmed in this project that whether B-RAFV600E mutation induce CPT1C expression through abating the microRNA-370, which negatively regulates CPT1C. We believe that implementation of this project will help to understand the molecular mechanism of thyroid carcinogenesis as well as provide clues for development of novel intervention against thyroid carcinomas.