lncRNA-miR210HG作为ceRNA调控非小细胞肺癌并发肺栓塞发病机制的研究

Pulmonary thromboembolism is one of the common complications of lung cancer, it is also the main reason of leading to the death of lung cancer patients. Oxygen-induced factor-1a (HIF1a) can induce vascular endothelial cell division and proliferation，which is the one of the pathogenesis mechanisms of non-small cell lung cancer (NSCLC) complicated with pulmonary embolism. MiRNA210 involves in the regulation of hypoxic cell biological function, but its regulatory mechanism is unclear. In this study, miR210HG was found to be differentially expressed in peripheral blood single nuclear cells of patients with NSCLC complicated with pulmonary embolism in Xinjiang Uygur and Han ethnic groups. MiR210HG plays an important role in mediating miR210 function. Therefore, we speculate that miR210HG is involved in the pathogenesis of NSCLC complicated with pulmonary embolism by regulating HIF-1a signaling pathway. To verify whether miRNA-210 directly targeting the signaling of PI3K / Akt / HIF-1a on the invasion and metastasis of cancer cells. Gene overexpression and silencing techniques were used in cells and nude mice NSCLC liver metastases model, respectively. Furthermore, its expression detection might be as one of the prognosis molecular markers for patients with NSCLC complicated with pulmonary embolism. This proposal will provide a new view to diagnosis and treatment the NSCLC complicated with pulmonary embolism in Xinjiang area, thereafter it also set the theoretical basis for its clinical transformation in NSCLC complicated with pulmonary embolism prevention and treatment.

肺血栓栓塞症是肺癌常见并发症之一，也是导致肺癌患者死亡的主要原因。低氧诱导因子-1a（HIF-1a）诱发血管内皮细胞分裂、増殖在肺癌合并肺栓塞机制中起重要作用，miRNA-210参与调控乏氧细胞生物学功能，但其调控机制不清。本课题组前期发现miR210HG在新疆维、汉两民族非小细胞肺癌并发肺栓塞患者外周血单个核细胞中存在差异表达，而miR210HG在实现miR210功能中起重要作用。因此我们推测miR210HG通过调控HIF-1a信号通路参与肺癌并发肺栓塞的发生。拟通过基因过表达及沉默技术，分别在细胞及裸鼠非小细胞肺癌肝转移模型上验证其是否直接靶向miRNA-210，通过PI3K/Akt/HIF-1a信号调控癌细胞的侵袭、转移。通过检测患者体内其水平的表达，判断其能否作为并发肺栓塞的非小细胞肺癌患者预后的分子标记物，以期为新疆地区该病诊治向临床转化打下理论基础，为其发病机制研究提供新思路。

肺血栓栓塞症（PTE）是肺癌常见并发症之一，也是导致肺癌患者死亡的主要原因。低氧诱导因子-1a（HIF-1a）诱发血管内皮细胞分裂、増殖在肺癌合并PTE机制中起重要作用，miRNA-210参与调控乏氧细胞生物学功能，但其调控机制不清。本课题组前期发现miR210HG在新疆维、汉两民族非小细胞肺癌（NSCLC）并发PTE患者外周血单个核细胞中存在差异表达，而miR210HG在实现miR210功能中起重要作用。因此我们推测miR210HG通过调控HIF-1a信号通路参与肺癌并发PTE的发生。拟通过基因过表达及沉默技术，分别在细胞及裸鼠NSCLC模型上验证其是否直接靶向miRNA-210，通过PI3K/Akt/HIF-1a信号调控癌细胞的侵袭、转移。通过检测患者体内其水平的表达，判断其能否作为并发肺栓塞的NSCLC患者预后的分子标记物，以期为新疆地区该病诊治向临床转化打下理论基础，为其发病机制研究提供新思路。结果发现：（1）很多关于肺癌合并肺栓塞差异表达的lncRNA和mRNA，其中MERGE.31027.6，MERGE.30976.2和ENST00000318988，ENST00000397519与肺癌合并肺栓塞的关系可能较大；（2）证实miRNA-210能够靶向HIF-1α，并促进细胞增殖，减慢细胞周期和凋亡,可以对肺癌的临床诊疗提供一定的帮助，为肺癌的临床诊治提供新的分子生物学标志物；（3）lncRNA-miR210HG可能作为ceRNA竞争性地与miRNA210结合，从而调控下游HIF-1α、VEGF的mRNA表达，参与NSCLC的发生、发展，并与肺癌的不良预后有关。