LncRNA mechanisms in cancer

LncRNA在癌症中的机制

• 批准号: 10212978
• 负责人: Howard Y Chang
• 金额: $ 87.15万
• 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/10212978
• 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 editing; 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.

项目摘要 Chang Lab具有长期非编码RNA（LNCRNA）为普遍的发现的发现 以及人类疾病中的重要监管因子，特别是在癌症中。 lncrnas可以用作 DNA和染色质修饰机械之间的接口，从而介导表观遗传 癌症的畸变。 lncrna热水大约三分之一的人过表达 乳腺癌是最终转移和死亡的有力预测指标。长期 该程序的目标是了解人类癌症中LNCRNA作用的机理基础。 我们的投资将解决（i）LNCRNA在驱动细胞对细胞表观遗传学中的作用 异质性是癌症转移和耐药性的关键问题，使用尖端 单细胞表观基因组技术和体内遗传模型； （ii）RNA的新兴角色 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查明驱动程序lncrna 人类癌的基因。这些实验将提供有关未编码多长时间的关键见解 RNA可能会激发癌症的进展，并为新的癌症诊断铺平道路 和将来的治疗方法。