LncRNA mechanisms in cancer

项目摘要 Chang实验室率先发现了长非编码RNA(LncRNAs)，作为一种普遍存在的 也是人类疾病的重要调节者，尤其是在癌症方面。InncRNA可以作为 DNA和染色质修饰机制之间的界面，从而介导表观遗传 癌症的畸变率。IncRNA HOTAIR在大约三分之一的人类中过度表达 乳腺癌，是最终转移和死亡的有力预测指标。从长远来看 这个项目的目标是了解lncRNA在人类癌症中作用的机制基础。 我们的研究将解决(I)lncRNAs在驱动细胞到细胞表观遗传学中的作用 异质性，癌症转移和治疗耐药性的关键问题，使用尖端技术 单细胞表观基因组技术和体内遗传模型；(Ii)RNA的新作用 癌症发展中的化学修饰；(Iii)改变RNA的非编码突变 结构(“核糖核酸”)并使用新的表观基因组编辑技术来精确定位驱动程序lncRNA 人类癌症中的基因。这些实验将提供关于非编码多长时间的关键见解 RNA可能会引发癌症的进展，并为新的癌症诊断铺平道路 以及未来的治疗方法。

Project Summary The Chang lab has pioneered discoveries of long noncoding RNAs (lncRNAs) as a pervasive and important class of regulators in human diseases, notably in cancer. LncRNAs can serve as the interface between DNA and chromatin modification machinery, and thus mediate epigenetic aberrations in cancer. The lncRNA HOTAIR is overexpressed in approximately a third of human breast carcinomas and is a powerful predictor of eventual metastasis and death. The long term goal of this program is to understand the mechanistic basis of lncRNA action in human cancers. Our investigations will address (i) the roles of lncRNAs in driving cell-to-to cell epigenetic heterogeneity, a critical issue in cancer metastasis and therapy resistance, using cutting edge single cell epigenomic technology and in vivo genetic models; (ii) the emerging roles of RNA chemical modifications in cancer development; (iii) noncoding mutations that change RNA structure (“ribosnitches”) and use new epigenome editing technologies to pinpoint driver lncRNA genes in human cancers. These experiments will provide key insights into how long noncoding RNAs may instigate cancer progression, and should pave the way for new cancer diagnostics and treatments in the future.