LncRNA mechanisms in cancer

项目摘要 Chang实验室率先发现了长非编码RNA（lncRNA）， 在人类疾病中也是重要的调节剂，特别是在癌症中。lncRNA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 癌症中的畸变lncRNA HOTAIR在大约三分之一的人类中过表达。 乳腺癌，是最终转移和死亡的有力预测因子。长期 该项目的目标是了解lncRNA在人类癌症中作用的机制基础。 我们的研究将解决（i）lncRNA在驱动细胞间表观遗传中的作用， 异质性是癌症转移和治疗抵抗中的关键问题， 单细胞表观基因组技术和体内遗传模型;（ii）RNA的新兴作用 癌症发展中的化学修饰;（iii）改变RNA的非编码突变 结构（“ribosniches”），并使用新的表观基因组编辑技术来精确定位驱动lncRNA 人类癌症的基因。这些实验将提供关键的见解， RNA可能会引发癌症进展，并为新的癌症诊断铺平道路 以及未来的治疗。

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.