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Updated: Nov 2, 2025
Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
Published on: February 21, 2014
Identification of epigenetic regulators in the estrogen signaling pathway via siRNA screening
Yun Ren1, Yan Liu, Hailin Wang
1State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China. hlwang@rcees.ac.cn.
Abstract:
Breast cancer is the most prevalent malignant disease among women across the globe. Notably, estrogen signaling plays a vital role in the progression of estrogen receptor-positive breast cancer. Therefore, targeting epigenetic regulators is a promising therapy for cancer. To identify epigenetic regulators, we conducted a siRNA screening targeting 140 epigenetic genes by which 32 positive and 15 negative regulators of estrogen signaling were obtained. The protein-protein interaction network of the candidate genes was constructed and the topological parameters of the network were calculated. As a result, the top 10 genes with higher MCC (Maximal Clique Centrality) scores were considered as hub genes. Notably, the hub genes all belong to polycomb group genes. The transcription levels of the above genes were compared between breast cancer and normal tissues using the UALCAN database. Then, the survival analysis of the hub genes was conducted using the Kaplan-Meier Plotter online database. Lastly, the effect of hub genes on MCF-7 cell proliferation and ER target gene expression were investigated. These results indicate that PcG genes regulate estrogen signaling and breast cancer development.
Insights
This study identifies key epigenetic regulators, specifically polycomb group genes, that influence estrogen signaling in breast cancer. These findings highlight potential new therapeutic targets for estrogen receptor-positive breast cancer.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Breast cancer is a leading global malignancy in women.
- Estrogen signaling is crucial for estrogen receptor-positive breast cancer progression.
- Targeting epigenetic regulators offers a promising therapeutic strategy.
Purpose of the Study:
- To identify novel epigenetic regulators of estrogen signaling in breast cancer.
- To investigate the role of these regulators in breast cancer development and progression.
Main Methods:
- Conducted siRNA screening of 140 epigenetic genes to identify regulators of estrogen signaling.
- Constructed a protein-protein interaction network and identified hub genes using Maximal Clique Centrality (MCC).
- Analyzed gene expression and survival data using UALCAN and Kaplan-Meier Plotter databases; assessed effects on MCF-7 cell proliferation and ER target gene expression.
Main Results:
- Identified 32 positive and 15 negative regulators of estrogen signaling.
- Top 10 hub genes with high MCC scores were identified as polycomb group (PcG) genes.
- PcG genes showed altered transcription levels in breast cancer tissues and correlated with patient survival.
- PcG genes significantly impacted MCF-7 cell proliferation and estrogen receptor target gene expression.
Conclusions:
- Polycomb group genes play a critical role in regulating estrogen signaling pathways.
- These PcG genes are implicated in the development and progression of breast cancer.
- PcG genes represent potential therapeutic targets for estrogen receptor-positive breast cancer.
