长链非编码RNA作为非小细胞肺癌分子标记物的筛选及其功能研究

Long non-coding RNA (lncRNA) is tentatively defined as non-coding RNAs more than 200 nucleotides, and characterized by its vital regulatory roles in biological activities including tumorigenesis. In our preliminary study, we performed the microarray lncRNA analysis of 12 non-small cell lung cancer (6 squamous cell carcinoma and 6 adenocarcinoma) and paired peritumor lung cancer. We found 20 differently expressed lncRNAs in NSCLC, which indicates more altered lncRNAs involved in NSCLC tumorigenesis. Our study aims to discover and validate NSCLC associated lncRNA biomarkers by microarray and quantitative RT-PCR. Moreover, the effects of the targeted lncRNA will be assessed by silencing and over-expressing the lncRNA in NSCLC cultured cells. The main contribution of this proposed research is to establish a panel of validated lncRNAs biomarkers for early diagnosis of NSCLC and elucidate the role of lncRNA in NSCLC for new drug development.

长链非编码RNA (lncRNA) 是一类转录长度超过200 nt的非编码RNA分子，能在多层面调控基因的表达，与肿瘤的发生发展密切相关。我们前期工作利用高通量Agilent芯片技术对12例非小细胞肺癌（鳞癌6例，腺癌6例）及12例配对癌旁组织进行全基因组lncRNA差异表达分析，已筛选出20个尚未见报道的在非小细胞肺癌中显著差异表达的lncRNA，提示lncRNA可能参与了非小细胞肺癌的发生发展过程。本项目拟通过实时荧光定量RT-PCR法，在200例非小细胞肺癌（鳞癌100例，腺癌100例）及配对癌旁组织中进一步验证芯片结果，确定候选lncRNA分子标记物，将其表达水平与临床病理资料、患者的预后进行关联分析，并利用RNA过表达和干扰技术对上述候选lncRNA进行深入的功能研究。