lncRNA NEAT1通过miR-454-3p/SLC2A1/GLUT1分子轴调控Warburg效应进而调控分化型甲状腺癌碘抵抗的机制研究

分化型甲状腺癌（DTC）是全球常见的内分泌恶性肿瘤之一，Warburg效应作为肿瘤细胞能量代谢的重要特征，与放疗抵抗密切相关，但Warburg效应调控机制尚未阐明。前期研究发现，Lnc NEAT1在放射性碘抵抗DTC细胞中高表达，荧光素酶实验证实Lnc NEAT1与miR-454-3p互作进而调控下游靶基因SLC2A1。SLC2A1及其编码的葡萄糖单向转运蛋白（GLUT1），已经证明与Warburg效应密切相关。我们推测：过表达Lnc NEAT1通过下调miR-454-3p及上调SLC2A1/ GLUT1，导致Warburg效应。项目进一步研究Lnc NEAT1调控Warburg效应影响放射性抵抗发生的机制。通过检测131I敏感以及131I抵抗患者的血液样本中的Lnc NEAT1、miR-454-3p、SLC2A1及GLUT1表达，找出两组患者的差异性。为临床治疗DTC放射抵抗提供新方案。

Differentiated thyroid carcinoma(DTC) is one of the most common endocrine malignancies in the world. Warburg effect, as an important feature of energy metabolism of tumor cells, not only promotes the proliferation and invasion of tumor cells, but also is closely related to the resistance to chemotherapy and radiotherapy. However, the regulatory mechanism of Warburg effect remains unclear. Previous studies have shown that Inc NEAT1 is highly expressed in radioactive iodine-resistant PTC cells, and the luciferase test confirmed that Inc NEAT1 will interact with miR-454-3p to regulate the downstream target gene SLC2A1.SLC2A1 and the key protein of glucose one-way transport (GLUT1) encoded by SLC2A1 have been proved to be closely related to the Warburg effect. We hypothesize that the overexpression of Inc NEAT1 will result in Warburg effect by down-regulating miR-454-3p and up-regulating SLC2A1/ GLUT1. We will further explore the mechanisms Inc NEAT1’s regulation on Warburg effect on the occurrence of radioactive resistance. The expression levels of Inc NEAT1, miR-454-3p, SLC2A1 and GLUT1 in blood samples of patients in 131I-sensitive group and 131I- resistant group will be tested, and the differences between the two groups will be explored. As a result, it will provide a new clinical treatment of DTC radiation resistance.