A systematic in silico mining of the mechanistic implications and therapeutic potentials of estrogen receptor (ER)-α in breast cancer

Xin Li; Rong Sun; Wanpeng Chen; Bangmin Lu; Xiaoyu Li; Zijie Wang; Jinku Bao

doi:10.1371/journal.pone.0091894

A systematic in silico mining of the mechanistic implications and therapeutic potentials of estrogen receptor (ER)-α in breast cancer

PLoS One. 2014 Mar 10;9(3):e91894. doi: 10.1371/journal.pone.0091894. eCollection 2014.

Authors

Xin Li¹, Rong Sun¹, Wanpeng Chen¹, Bangmin Lu¹, Xiaoyu Li¹, Zijie Wang¹, Jinku Bao¹

Affiliation

¹ School of Life Sciences and Key Laboratory of Bio-Resources and Eco-Environment, Ministry of Education, Sichuan University, Chengdu, China.

Abstract

Estrogen receptor (ER)-α has long been a potential target in ER-α-positive breast cancer therapeutics. In this study, we integrated ER-α-related bioinformatic data at different levels to systematically explore the mechanistic and therapeutic implications of ER-α. Firstly, we identified ER-α-interacting proteins and target genes of ER-α-regulating microRNAs (miRNAs), and analyzed their functional gene ontology (GO) annotations of those ER-α-associated proteins. In addition, we predicted ten consensus miRNAs that could target ER-α, and screened candidate traditional Chinese medicine (TCM) compounds that might hit diverse conformations of ER-α ligand binding domain (LBD). These findings may help to uncover the mechanistic implications of ER-α in breast cancer at a systematic level, and provide clues of miRNAs- and small molecule modulators- based strategies for future ER-α-positive breast cancer therapeutics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Algorithms
Breast Neoplasms / drug therapy*
Breast Neoplasms / genetics
Computer Simulation*
Data Mining*
Drugs, Chinese Herbal / therapeutic use
Estrogen Receptor alpha / metabolism*
Female
Gene Expression Regulation, Neoplastic
Gene Ontology
Humans
MicroRNAs / metabolism
Molecular Dynamics Simulation
Molecular Sequence Annotation
Protein Binding
Protein Structure, Tertiary
Reproducibility of Results

Substances

Drugs, Chinese Herbal
ESR1 protein, human
Estrogen Receptor alpha
MicroRNAs

Grants and funding

This study was supported in part by the National Natural Science Foundation of China (No. 81173093, No. 30970643, and No. J1103518), the Special Program for Youth Science and the Technology Innovative Research Group of Sichuan Province, China (No. 2011JTD0026). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.