靶向ADAM15的长链非编码RNA（lncRNA1308）调控云南宣威肺癌(XWLC)生物学行为的分子机制研究

长链非编码RNAs被证实在癌症的发生、发展过程中发挥重要的功能。本研究组前期对云南宣威地区的人肺癌和癌旁组织以及从宣威肺癌细胞系XWLC-05的基因组表达数据的发掘和分析，通过UCSC、NONCODEV3、lncRNAdb等数据库对lncRNA的注释和定义标准，新发现了一个表达差异显著、长度约为525个碱基的lncRNA片段与ADAM15的启动子区存在200个以上的碱基互补配对关系且与ADAM15的表达呈正相关。本课题拟通过荧光素酶共转染等实验探讨该差异lncRNA（lncRNA1308）是如何通过cis作用元件、转录因子/染色质修饰复合物、结合蛋白、microRNAs等方式，实现对ADAM15的靶向调控，探究其表达变化对肺癌细胞增殖、侵袭的影响，并在动物模型上验证其对肿瘤生长的作用。本项目的开展将为云南宣威肺癌发生、发展和复发转移的干预及其早期诊断和治疗提供新靶点和新策略。

The long noncoding RNAs (lncRNAs) have been proven to play important roles in the development and progression of cancer. Recently, through exploring and analyzing the global gene expression profile from human lung cancer and adjacent tissues and lung cancer cell line XWLC-05 genome, a new long noncoding RNA fragment which has significant difference of expression in cancer tissues and adjacent ones was identified according to the notes and standard definition of UCSC, NONCODEV3, lncRNAdb and other lncRNA database. This 525-base lncRNA fragment has more than 200 complementary bases pairing to the promoter region of ADAM15 and its expression level was positively correlated with ADAM15.In this project, luciferase co-transfection, CHIP, RIP and other methods are to be adopted to investigate how this special lncRNA (lncRNA1308) regulates the target ADAM15 by cis -acting elements, transcription factor/chromatin modification complexes, binding proteins, or microRNAs , etc. To explore its different expression influence on lung cancer cell proliferation, invasion, and verify its effect on tumor growth in animal models. The project will provide new targets and new strategies for the intervention and early diagnosis and treatment of the progress, development, recurrence and metastasis of Xuanwei lung cancer in Yunnan province.