促进肿瘤生长的长链非编码RNA SNHG1机制研究

The ENCODE program revealed that about 75% of the human genome was transcribed, but only less than 2% was the protein coding region, most of which were non-coding RNAs. In the last ten years, more and more studies have revealed that lond non-coding RNA(lncRNA) is associated with a series of major diseases, with tumors most prominent. In this project, through the tumor microarry expression data and TCGA tumor expression profile data, we screened one lncRNA SNHG1 which is highly expressed in tumor compaired to adjacent normal tissues. In previous studies, we discovered that SNHG1 mailny exists in the chromatin region of the nucleus, and the expression may be regulated by MYC, and can promote cell proliferation in vitro. We also discovered that SNHG1interacts with several DNA binding proteins and RNA splicing proteins. In this project, combing molecular and cell biology, high-throughput RNA-seq and ChIRP-seq technology with bioinformatic technology, we attempt to explore the function of SNHG1 in tumor genesis and development, and to study the mechanism by which SNHG1 was combined with DNA to regulate gene expression, and the mechanism by which SNHG1 was bound to pre-mRNA to regulate alternative splicing. This study will deepen the understanding of the role of lncRNAs in tumor genesis and development.

ENCODE计划揭示人类基因组约75%的区域发生转录，但只有不到2%的蛋白质编码区，这些转录本中大部分为非编码RNA。最近十年，越来越多的研究发现长链非编码RNA（lncRNA）与一系列重大疾病相关，其中以肿瘤最为突出。本项目通过实验室自产肿瘤表达谱芯片数据和公共的TCGA肿瘤表达谱测序数据，筛选了一条在多种肿瘤中都高表达的lncRNA SNHG1作为研究对象。在前期研究中发现，SNHG1主要存在于细胞核的染色质区域，表达可能受MYC调控，能在体外促进细胞增殖；SNHG1可与多种DNA结合蛋白和RNA splicing蛋白相互作用。本项目将结合分子细胞，高通量RNA-seq、ChIRP-seq和生物信息学等方法，探索SNHG1在肿瘤发生发展中的功能，并研究SNHG1与DNA结合调节转录，与pre-mRNA结合调节可变剪切的具体分子机制。此研究将加深对lncRNA在肿瘤发生发展中作用的认识。

ENCODE计划揭示人类基因组约75%的区域发生转录，但只有不到2%的蛋白质编码区，这些转录本中大部分为非编码RNA。最近十年，越来越多的研究发现长链非编码RNA（lncRNA）与一系列重大疾病相关，其中以肿瘤最为突出。本项目按计划研究了一条在多种肿瘤中都高表达的lncRNA SNHG1在肿瘤发生发展中功能和机制。研究发现SNHG1可以促进癌细胞生长。在机制方面，SNHG1通过影响AKT丝氨酸473位点的磷酸化水平从而促进AKT的激活，进而促进细胞生长。本项目还更新了包括SNHG1的非编码与大分子互作数据库NPInter。这些结果表明长链非编码RNA是重要的生物学分子，参与肿瘤等重大疾病，研究长lncRNA有助于了解疾病，并为疾病治疗、预防提供帮助。