WFDC21P及相关miR-628在肺腺癌发生及诊断中的临床价值

Secreted miRNAs and lncRNAs play important roles in the tumorigenesis and diagnosis of lung cancer. However, the specific molecular mechanism of their roles needs to be further studied deeply, and the diagnostic value should be further explored. The interaction and regulation between miRNAs and lncRNAs in tumor are hot research topics for scientists..In the previous studies of secreted miRNAs and their role in regulating gene expression, we found that miR-628 plays an important role in the diagnosis for lung adenocarcinoma, and it can suppress lung adenocarcinomia cell proliferation by regulating WFDC21P. By technologies of bioinformatics, molecular biology and immunology in this study, we will further explore the roles of miR-628 and WFDC21P in the diagnostics for lung adenocarcinoma, the action of miR-628 in directly regulating WFDC21P, and the mechanism of miR-628 in regulating WFDC21P and STAT3-related factors. We will also investigate the effect of these factors on the proliferation and migration of lung adenocarcinoma cells to explore their roles in the diagnosis of lung adenocarcinoma. Our study will provide the new clinical diagnostic markers and targets for the diagnostics and therapy of lung adenocarcinoma.

分泌型miRNA、lncRNA在肺癌的发病及诊断中具有重要的临床价值；但其具体作用机理需要深入研究、其诊断价值需进一步开发。miRNAs与lncRNAs相互作用及调控，是目前肿瘤研究领域的热点。. 前期对分泌型miRNA及功能的研究中，我们发现分泌型miR-628在肺腺癌的诊断中发挥重要作用，通过调节WFDC21P表达，能有效抑制肺癌细胞增殖。本项目利用生物信息学、分子生物学、免疫学等相关分析技术，进一步探索WFDC21P及相关miR-628在肺腺癌发生及诊断中的重要作用，深入研究分泌型miR-628与WFDC21P在肺腺癌诊断中的作用、miR-628对WFDC21P的直接靶向调控作用、miR-628靶向WFDC21P对STAT3等相关因子的作用及机理等，探讨这些因子对肺腺癌细胞增殖、迁移的影响，及其在肺腺癌诊断中的临床价值，以期为肺腺癌的临床诊断及治疗提供新靶点和新的治疗方法。

分泌型miRNA、lncRNA在肺癌的发病及诊断中具有重要的临床价值；但其具体作用机理需要深入研究、诊断价值需进一步开发。miRNAs与lncRNAs相互作用及调控，是目前肿瘤研究领域的热点，目前有关WFDC21P报道甚少。.本项目发现（1）肺腺癌患者血清miR-628表达量降低，WFDC21P表达明显增高，二者表达水平呈负相关，可作为肺腺癌诊断的指标之一。吸烟因素是诱发肺腺癌发生的主要危险因素之一，吸烟者发生肺腺癌概率是不吸烟者的3.067倍。（2）过表达WFDC21P，磷酸化STAT3的水平明显升高。miR-628与WFDC21P可相互结合作用，miR-628能调节WFDC21P的表达及相关STAT3通路。miR-628能抑制肺癌细胞的增殖和迁移，而WFDC21P可促进了细胞增殖和迁移。二者影响肺癌细胞迁移机制与调控E-cadherin、N-cadherin、Snail表达有关。（3）动物实验模型实验研究表明，慢病毒lv-WFDC21P稳定表达可导致肿瘤体积和重量的明显增加；Lv-siRNA-WFDC21P处理组，肿瘤生长受到明显抑制。与对照组相比，慢病毒miR-628处理抑制了移植瘤体积和重量增加。WFDC21P过表达组，移植瘤中WFDC21P、p-STAT3、N-cadherin、Snail表达增加，E-Cadherin表达减少。MiR-628处理组，p-STAT3、N-cadherin、Snail表达量减少，E-Cadherin表达增高。总之，本项目研究了分泌miR-628与WFDC21P在肺腺癌诊断中的作用、miR-628对WFDC21P的靶向调控作用、miR-628靶向WFDC21P对STAT3等相关因子的作用及机理等，探讨了这些因子对肺腺癌细胞增殖、迁移等影响，及其在肺腺癌诊断中的临床价值，为肺腺癌的临床诊断治疗及药物设计提供了新靶点。