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Epigenomics-based identification of oestrogen-regulated long noncoding RNAs in ER+ breast cancer

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Version 3 2020-10-15, 21:00
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posted on 2020-10-15, 21:00 authored by Zhao Zhang, Wei Yu, Dan Tang, Yufan Zhou, Mingjun Bi, Hu Wang, Yan Zheng, Mingqiu Chen, Li Li, Xinping Xu, Wei Zhang, Huimin Tao, Victor X. Jin, Zhijie Liu, Lizhen Chen

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.

Funding

Z.L. is a CPRIT Scholar in Cancer Research. This work was supported by funds from CPRIT RR160017 to Z.L., V Foundation V2016-017 to Z.L., V Foundation DVP2019-018 to Z.L., Voelcker Fund Young Investigator Award to Z.L., UT Rising STARs Award to Z.L., Susan G. Komen CCR Award CCR17483391 to Z.L., NCI U54 CA217297/PRJ001 to Z.L.,‬PRIT the San Antonio Nathan Shock Center (NIA grant 3P30 AG013319-23S2) to L.C.Research reported in this publication was also supported by the NIGMS of the NIH under Award Number R01GM137009 to Z.L. and L.C. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. ‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬National Institute of General Medical Sciences [R01GM137009];

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