LncRNA SNHG8通过组蛋白H1调控染色质结构及其在乳腺癌中的作用

在前期研究工作中，课题申请人通过一套基于细胞特异性分数的筛选策略，鉴定了一批富集于上皮细胞的lncRNA，并聚焦于尚知之甚少的SNHG8。我们发现在乳腺癌病人肿瘤组织尤其是恶性程度高的肿瘤组织中，SNHG8表达降低。尤其有趣的是，该lncRNA呈现染色质定位并主要与链接组蛋白（linker histone）H1结合，并通过对组蛋白H1与染色质亲和力的调节，参与染色质高级结构的调控。本课题将以这些重要发现为基础，以乳腺癌为模型，继续研究“SNHG8-组蛋白H1-染色质构象改变”这一通路在正常上皮细胞向肿瘤细胞转化过程中所发生的调变及所发挥的作用。这些研究不仅将揭示lncRNA参与肿瘤发生的新机制，还可望为染色质构象改变与肿瘤发生的关系提供新的证据。

It is a frontier topic in the biological field on how to identify and functionally annotate lncRNAs with important functions. This applier has been working on screening of cancer-related genes by using bioinformatic strategies for many years. In an attempt to find lncRNAs involved in the malignant transition of epithelial cells, this applier set out to screen epithelial-enriched lncRNAs by using a cell type specific score (CTSS)-based pipeline, and chose to focus on one of the candidates SNHG8. Further analysis revealed that SNHG8 is mainly chromatin localized and manifests strong interaction with linker histone H1. More importantly, through modulating the affinity between histone H1 and chromatin DNA, SNHG8 is involved in the regulation of the higher structure of chromatin. On the basis of these important findings, this project will continue to investigate the role and regulation of "SNHG8-histone H1-chromatin structure" pathway during malignant transition of epithelial cells by using breast cancer as a model. We believe that our study will not only reveal a novel lncRNA-conducted mechanism in the pathogenesis of cancer, but also shed light on the relationship between chromatin structure changes and tumorigenesis.