多氯联苯（PCBs）蓄积于人体，引起甲状腺组织损伤，机制未明。我们发现，PCB118诱导甲状腺细胞超微结构改变，微管蛋白基因Tubb3和死亡相关蛋白激酶（DAPK）异常。已知Tubb3能激活DAPK自噬通路导致细胞解离，而长链非编码RNA（LncRNA）参与调控甲状腺损伤。通过基因芯片且证实，PCB118引起甲状腺LncRNA-NONRATT014386表达上调，Tubb3mRNA下降。生物信息学预测NONRATT014386位于Tubb3基因启动子区。据此假设，PCBs致甲状腺Tubb3表达异常受NONRATT014386调控；异常Tubb3激活DAPK/PKD/Vps34自噬通路导致甲状腺细胞超微结构损害。课题拟通过体内/体外模型、基因芯片与数据分析、Pull-down分析等，探讨LncRNA调控Tubb3在PCBs致甲状腺细胞自噬损伤中的新机制，为寻找甲状腺疾病高流行病因提供依据。

Polychlorinated biphenyl 118(PCB118) act as one typical types of polychlorinated biphenyls(PCBs) which could be absorbed and preserved permanently in organism. It is well established that PCBs disturb every point of thyroid hormone including synthetize and secretion, transportation and metabolism causing from the high similarity of thyroxine(T4). Recent evidence declared from ours that PCB118 induced thyrocytes dysfunction through PI3K/AKT/FoxO3a pathway and decreased secretion of T4. In addition, the existing proofs revealed that PCB118 produced abnormality of thyroidal ultrastructure, and even more than remarkable, it reduced expression of Tubb3, one of the important genes of β-tubulin, which play the key role in maintaining cell morphology. Meanwhile, it was also found that death associated protein kinase(DAPK) increased consistently. Since it was disclosed that Tubb3 could active DAPK pathway and induce cell autophagy, while LncRNA act as pivotal regulators leading to kinds of thyroidal diseases, in the course of our studies, when we used application of high throughput microarray analysis, we found PCB118 caused increasing of LncRNA-NONRATT014386, which accordance with the decreasing of Tubb3, and this phenomenon was verified in FRTL-5 cells. Furthermore, it was predicted that NONRATT014386 may locate in the activated area of Tubb3 with bioinformatics analysis technique. To data, we hypothesis that PCB118 could induce abnormal expression of Tubb3 and its protein of β-tubulin through NONRATT014386, then the aberrant Tubulin activates cell autophagy system through DAPK/PKD/Vps34 pathway, and induced disruption of thyroidal ultrastructure. In this project, we would utilize a series of molecular biological techniques such as western-blot, immunofluorescence, siRNA, RNA immunoprecipitation, microarray analysis and GST pull-down assay to discuss the mechanism of PCB118 induced abnormality of thyrocytes ultrastructure through LncRNA-NONRATT014386 regulated Tubb3, thus we hope to provide a novel approach in preventing environmental disrupting thyroidal diseases.