G-四链体介导的吲哚啉衍生物对Spns2癌转移基因的调控及其对人非小细胞肺癌的抑癌转移能力研究

肺癌是我国死亡人数最高的恶性肿瘤，其中80-90%的肺癌患者的死亡是由转移引起的。因此，寻找和针对关键抑癌转移靶标，深入探讨非小细胞肺癌转移的分子机制，一直是非常重要的科学问题。Spns2基因代表了一个新的治疗癌转移的靶标，针对这个靶标的药物可以帮助减少或防止体内肿瘤的转移。已开展的研究表明Spns2 mRNA富G序列易形成特殊结构的G-四链体，而G-四链体的形成可以明显地下调Spns2的表达。在本项目中，我们拟采用G-四链体介导的吲哚啉衍生物实现对Spns2基因表达的调控，进而抑制人非小细胞肺癌迁徙转移的能力。我们将系统研究吲哚啉衍生物对Spns2相关G-四链体的特异性识别能力，阐释吲哚啉衍生物通过靶向Spns2相关G-四链体来调控Spns2基因表达水平的分子机制，以核酸二级结构G-四链体为桥梁搭建Spns2基因与癌转移的关系，为研发高效、安全的抗癌转移的药物提供理论基础。

Lung cancer is the most common malignant tumor in China, and 80-90% of lung cancer patients are caused by metastasis. Therefore, it is always a very important scientific issue to find and target the key tumor suppressor metastasis targets and to explore the molecular mechanism of non-small cell lung cancer metastasis. The Spns2 gene represents a new target for the treatment of cancer metastasis, and the designed drugs targeting to it can help reduce or prevent tumor metastasis in vivo. Our studies have shown that rich G sequences in Spns2 mRNA is susceptible to atypically parallel G-quadruplex with a two-layer G-tetrad, while the formation of G-quadruplex could down-regulate Spns2 expression obviously. In this project, we intend to use G-quadruplex-mediated Indolizine derivatives to regulate the expression of Spns2 gene, thereby inhibiting the migration of human non-small cell lung cancer. We will systematically study the specific recognition ability of Indolizine derivatives for Spns2-related G-quadruplex, and explain the molecular mechanism of the regulation of Spns2 gene by G-quadruplex-mediated Indolizine derivatives. The nucleic acid G-quadruplex bridges the relationship between Spns2 gene and cancer metastasis, and provides a theoretical basis for the development of a new and effective drug candidate for anti-cancer metastasis.