microRNA-195调控转录因子Sox4介导的上皮间质转化在云南高发女性肺癌侵袭和转移中的研究

云南宣威女性肺癌的发病率和死亡率位列全球首位，是全球点状区域性高发肺癌、与室内污染相关肺癌研究的代表性疾病，复发和转移是患者死亡的主要原因。上皮间质转化（EMT）是肿瘤发生转移的前提，microRNA对该过程有关键的调控作用。大样本高通量芯片分析揭示，miR-195是宣威女性肺癌中特异性表达降低的microRNA，转录因子Sox4是其重要的靶基因。Sox4与肿瘤细胞恶性生物学行为及EMT密切相关.本研究拟通过临床样本检测、双荧光素酶报告实验、RNA干扰及过表达、细胞侵袭转移实验、构建动物模型等手段，研究miR-195与Sox4的临床意义和表达的相关性，miR-195对宣威女性肺癌上皮间质转化的影响及作用机制，从分子、细胞及器官水平揭示宣威地区女性肺癌患者存在"miR-195→Sox4→EMT→肺癌侵袭转移"分子生物学事件，为研发高发区女性肺癌转移预警标志和潜在的干预治疗靶点提供实验依据。

The incidence and mortality rate of Yunnan Xuanwei female lung cancer ranks first in the world, which is the representative of regional lung cancer and indoor pollution-related disease. Recurrence and metastasis are the main causes of death in patients. Epithelial mesenchymal transition (EMT) is a prerequisite for tumor metastasis and microRNA has a key role in the process of EMT. A large sample of high throughput microarray analysis revealed miR-195 is specificlly reduced in Xuanwei female lung cancer and Sox4 was a key target gene of miR-195. Sox4 is closely related with cell malignant biological behaviors and EMT. This study will research the correlation between miR-195 and Sox4, and the effect of miR-195 on the mechanism of epithelial mesenchymal transformation in Xuanwei female lung cancer through the clinical sample detection, dual luciferase reporterassay, RNA interference and over expression experiments,cell invasion and metastasis assay and animal model construction method. The work will reveal the molecular event of "miR-195→Sox4→EMT→invasion and metastasis of lung cance" in Xuanwei female lung cancer from molecular, cell and organ level ,which will provide important experimental evidence for develop early metastasis diagnostic biomarker and potential intervention or therapeutic target in areal female lung cancer with high incidence .