肺癌是世界上最常见的恶性肿瘤之一。目前非手术治疗存在化疗药物抵抗，耐药以及敏感性低等问题。研究表明，澳洲茄边碱对包括肺癌在内的多种肿瘤具有抗癌活性。我们前期结果表明，长链非编码RNA-HOTAIR和miR-214-3p可能介导澳洲茄边碱对肺腺癌的生长抑制效应，且miR-214-3p可直接靶向调控核转录因子SP1的蛋白表达，进而刺激IGFBP1的表达和活性，最终抑制肺腺癌的生长和转移。为深入明确其具体的分子机制及调控网络，本项目拟进行：1）体外实验研究HOTAIR/miR-214-3p/SP1/IGFBP1信号通路在澳洲茄边碱抑制肺腺癌生长中的关键作用；探索HOTAIR，miR-214-3p与SP1和IGFBP1等蛋白之间的相互作用及调控机制；2）建立裸鼠肿瘤模型，体内观察澳洲茄边碱对肺腺癌的生长抑制效应，明确HOTAIR，miR-214-3p和IGFBP1等异常表达对肺腺癌生长表型的影响。

Lung cancer is one of the most common malignant tumors in the world. The non-surgical treatment still faces chemotherapy drug resistance, toxicities,low sensitivity and other adverse issues. The large numbers of studies show that solamargine has anti-cancer effect for a wide variety of tumor including lung cancer. Our previous work showed that lncRNA-HOTAIR and miR-214-3p might mediate the effect of solamargine-inhibited lung cancer cell growth. Moreover，SP1 was a direct target of miR-214-3p，overexpression of miR-214-3p upregulated the IGFBP1 protein expression by suppressing the SP1 protein expression，finally，inhibited the cell growth and metastasis of lung cancer. To further clarify the specific molecular mechanism and regulatory network，this project will conduct research from the following two aspects: 1) The use of modern molecular biology techniques, explore the potential molecular mechanisms which solamargine inhibited the cell growth and metastasis in non small cell lung carcinoma (NSCLC)，and illuminate the key role of lncRNA-HOTAIR/miR-214-3p/SP1/IGFBP1 Signaling pathways in solamargine-inhibited cell growth. To explore the effect of lncRNA-HOTAIR on miR-214-3p，and the interaction between lncRNA-HOTAIR and SP1 or IGFBP1 protein. 2) In animal model, to observe the inhibition effect of solamargine on lung cancer tissues with up/down-regulate the expression of the lncRNA-HOTAIR，miR-214-3p and IGFBP1.