顺铂是非小细胞肺癌（NSCLC）一线治疗药物，其耐药性的产生是临床亟待解决的重大难题。我们前期发现LncRNA SFTA1P（SFTA1P）具肺组织特异性，其可通过抑制DNA损伤修复（DDR）通路活性，增敏顺铂诱导细胞凋亡。进一步预实验显示TGF-β可显著下调SFTA1P表达，进而使DDR通路活性增加，促进NSCLC顺铂耐药，但作用机制尚不清楚。我们推测SFTA1P可能为TGF-β/DDR通路关键介导因子，通过调控DDR通路基因表达下调其活性，实现逆转NSCLC顺铂耐药。本课题拟：①体内外实验进一步研究SFTA1P经TGF-β/DDR途径介导NSCLC顺铂耐药的作用；②明确SFTA1P靶基因和靶蛋白并阐明其调控机制；③通过临床样本验证TGF-β/SFTA1P/DDR通路与顺铂耐药的相关性，探讨其临床意义。本课题完成将为NSCLC顺铂耐药预测及精准干预提供新依据和潜在特异性靶标。

Cisplatin is a first-line treatment for non-small cell lung cancer (NSCLC), but the drug resistance is a major problem for the treatment of NSCLC. Our previous studies found that LncRNA SFTA1P (SFTA1P) was a lung-specific high expression gene，and it could increase cisplatin-induced apoptosis by inhibiting the activity of DNA damage repair (DDR) pathway. Further experiments showed that TGF-β significantly down-regulated the expression of SFTA1P and increased the activity of the DDR pathway, then promoted cisplatin resistance in NSCLC. However, its mechanism remains unclear. Based on previous study, we propose the hypothesis that SFTA1P is a key mediator of the TGF-β/DDR pathway, which can inhibit the activity of DDR pathway and then reverse NSCLC cisplatin resistance ultimately. In the present study, we will first use cellular and animal models to determine the role of SFTA1P in TGF-β/DDR pathway mediated NSCLC cisplatin resistance. Secondly, we will further explore the target gene and target protein of SFTA1P and elucidate its regulatory mechanism. Finally, the clinical significance of this study will be verified in NSCLC clinical samples. This project will provide new theoretical basis and potential specific molecular target for prediction and precise intervention NSCLC cisplatin resistance.