STAT3调控lncRNA HOTAIR介导炎症诱导EMT在吸烟所致COPD和肺癌中的作用及干预研究

项目名称： STAT3调控lncRNA HOTAIR介导炎症诱导EMT在吸烟所致COPD和肺癌中的作用及干预研究

项目编号： No.81473011

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 刘起展

作者单位： 南京医科大学

项目金额： 80万元

中文摘要： 吸烟是一种严重危害人类健康的不良生活方式；慢性阻塞性肺病(COPD)和肺癌是吸烟最常见和最严重的疾病，但其发病机制不清楚。长链非编码RNA(lncRNA)具有重要生物学功能，而其在环境污染物所致损伤中作用及机制研究报道甚少。本项目在已建立香烟烟雾抽提物(CSE)所致肺HBE细胞炎症、上皮间质转化(EMT)和恶性转化模型基础上，分别应用IL-6中和抗体、STAT3抑制剂或siRNA、正义或反义lncRNA HOTAIR及丹参酮IIA和三羟基异黄酮等处理CSE所致HBE细胞急性损伤和恶性转化模型，香烟烟雾所致COPD和肺癌动物模型及不同程度吸烟人群队列，从正向和反向在细胞、动物和人群探讨STAT3调控lncRNA HOTAIR介导炎症诱导EMT在吸烟所致COPD和肺癌中作用及干预效果，以揭示吸烟所致COPD和肺癌的部分分子机制、为寻找吸烟所致肺损伤的早期生物标志及发现新的防控措施提供科学依据。

中文关键词： 吸烟；化学致癌；表观遗传；分子机制；上皮间质转化

英文摘要： Cigarette smoking is one of unhealthy lifestyles that threatens seriously human's health. The chromic obstructive pulmonary disease (COPD) and lung cancer are the most common and serious diseases induced by smoking, respectively, however, their molecular mechanisms remain unclear. Long non-coding RNA (lncRNA) has many important biological functions, but there are very few investigative publications about the roles and mechanisms of lncRNA in the damages induced by environmental pollution. Based on our preliminary results that CSE-induced inflammation, epithelial-mesenchymal transition (EMT), and the malignant transformation of human bronchial epithelial (HBE) cells, we are going to investigate the roles and interventions of inflammation to EMT mediated by STAT3-regulated lncRNA HOTAIR in cigarette smoking-induced COPD and lung cancer on the levels of cell, animal, and population, respectively, by using the following three models. (i) Cell model, treatmemt of HBE cells by CSE in the presence or absence of IL-6-neutralizing antibody, STAT3 inhibitor or siRNA, lncRNA HOTAIR siRNA or plasmid, Tan IIA, and Genistein, respectively; (ii) The Bal/c mice and Wistar rat models of COPD and tumorigenesis induced by cigarette smoke in the present or absent of Tan IIA or Genistein; (iii) Cohort study on population with different smoking levels. Our results will be helpful to understand the molecular mechanisms underlying smoking-induced COPD and lung cancer, which will provide new clues to find the early biomarkers and new measures of preventing and controling the smoking-induced lung damage.

英文关键词： cigarette smoking;chemical carcerogenesis;epigenetic;molecular mechanism;epithelial-mesenchymal transition