LncRNA mechanisms in cancer

LncRNA在癌症中的机制

• 批准号: 10449099
• 负责人: Howard Y Chang
• 金额: $ 95.45万
• 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/10449099
• 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.

项目总结

项目成果

Inducible lncRNA transgenic mice reveal continual role of HOTAIR in promoting breast cancer metastasis.

• DOI: 10.7554/elife.79126
• 发表时间: 2022-12-29
• 期刊: ELIFE
• 影响因子: 7.7
• 作者: Ma, Qing;Yang, Liuyi;Tolentino, Karen;Wang, Guiping;Zhao, Yang;Litzenburger, Ulrike M.;Shi, Quanming;Zhu, Lin;Yang, Chen;Jiao, Huiyuan;Zhang, Feng;Li, Rui;Tsai, Miao-Chih;Chen, Jun-An;Lai, Ian;Zeng, Hong;Li, Lingjie;Chang, Howard Y.
• 通讯作者: Chang, Howard Y.

Personal regulome navigation of cancer.

• DOI: 10.1038/s41568-021-00381-x
• 发表时间: 2021-10
• 期刊: Nature reviews. Cancer

Enhanced T cell effector activity by targeting the Mediator kinase module.

通过靶向介体激酶模块来增强T细胞效应子活性。

• DOI: 10.1126/science.abn5647
• 发表时间: 2022-11-11
• 期刊: Science (New York, N.Y.)

Preleukemic Hematopoietic Stem Cells in Human Acute Myeloid Leukemia.

• DOI: 10.3389/fonc.2017.00263
• 发表时间: 2017
• 期刊: Frontiers in oncology
• 影响因子: 4.7
• 作者: Corces MR;Chang HY;Majeti R
• 通讯作者: Majeti R

Long Noncoding RNAs: At the Intersection of Cancer and Chromatin Biology.

• DOI: 10.1101/cshperspect.a026492
• 发表时间: 2017-07-05
• 期刊: Cold Spring Harbor perspectives in medicine
• 影响因子: 5.4
• 作者: Schmitt AM;Chang HY
• 通讯作者: Chang HY