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Epigenomics-based identification of oestrogen-regulated long noncoding RNAs in ER+ breast cancer. RNA Biol 2020 Nov;17(11):1590-1602

Date

06/09/2020

Pubmed ID

32506995

Pubmed Central ID

PMC7567493

DOI

10.1080/15476286.2020.1777769

Scopus ID

2-s2.0-85087143219 (requires institutional sign-in at Scopus site)   10 Citations

Abstract

Breast cancer is one of the most prevalent cancers in women worldwide. Through the regulation of many coding and non-coding target genes, oestrogen (E2 or 17β-oestradiol) and its nuclear receptor ERα play important roles in breast cancer development and progression. Despite the astounding advances in our understanding of oestrogen-regulated coding genes over the past decades, our knowledge on oestrogen-regulated non-coding targets has just begun to expand. Here we leverage epigenomic approaches to systematically analyse oestrogen-regulated long non-coding RNAs (lncRNAs). Similar to the coding targets of ERα, the transcription of oestrogen-regulated lncRNAs correlates with the activation status of ERα enhancers, measured by eRNA production, chromatin accessibility, and the occupancy of the enhancer regulatory components including P300, MED1, and ARID1B. Our 3D chromatin architecture analyses suggest that lncRNAs and their neighbouring E2-resonsive coding genes, exemplified by LINC00160 and RUNX1, might be regulated as a 3D structural unit resulted from enhancer-promoter interactions. Finally, we evaluated the expression levels of LINC00160 and RUNX1 in various types of breast cancer and found that their expression positively correlated with the survival rate in ER+ breast cancer patients, implying that the oestrogen-regulated LINC00160 and its neighbouring RUNX1 might represent potential biomarkers for ER+ breast cancers.

Author List

Zhang Z, Yu W, Tang D, Zhou Y, Bi M, Wang H, Zheng Y, Chen M, Li L, Xu X, Zhang W, Tao H, Jin VX, Liu Z, Chen L

Author

Victor X. Jin PhD Professor in the Institute for Health and Equity department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Apoptosis
Biomarkers, Tumor
Breast Neoplasms
Cell Line, Tumor
Computational Biology
Enhancer Elements, Genetic
Epigenesis, Genetic
Estrogen Receptor alpha
Estrogens
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Immunophenotyping
RNA, Long Noncoding
Receptors, Estrogen
Response Elements
Signal Transduction
Transcription, Genetic
Transcriptome