LncRNA mechanisms in cancer

LncRNA在癌症中的机制

• 批准号: 9325477
• 负责人: Howard Y Chang
• 金额: $ 97.4万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-03 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9325477
• 关键词: Address; Automobile Driving; Breast Carcinoma; Cancer Control; Cancer Diagnostics; Cancer Etiology; Cancer Patient; Cells; Cessation of life; Chemicals; DNA Modification Process; Development; Epigenetic Process; Future; Genes; Genetic Models; Goals; Heterogeneity; Human; Investigation; Malignant Neoplasms; Mediating; Modification; Mutation; Neoplasm Metastasis; RNA; Research; Resistance; Risk Assessment; Role; Site; Structure; Technology; Untranslated RNA; Woman; cancer therapy; chromatin modification; epigenome; epigenomics; experimental study; human disease; improved; in vivo; insight; malignant breast neoplasm; overexpression; programs; targeted cancer therapy; tumor progression

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.

项目概要 Chang 实验室率先发现了长非编码 RNA (lncRNA) 作为一种普遍存在的 LncRNA 是人类疾病（特别是癌症）中的一类重要调节因子。 DNA 和染色质修饰机制之间的界面，从而介导表观遗传 lncRNA 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因子。 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耐药性的一个关键问题，利用尖端技术 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（“ribosnitches”）并使用新的表观基因组编辑技术来精确定位驱动lncRNA 这些实验将为了解人类癌症中的基因非编码持续多久提供重要见解。 RNA 可能会促进癌症进展，并为新的癌症诊断铺平道路 以及今后的治疗方法。