Identification of epigenetic regulators in the estrogen signaling pathway via siRNA screening.

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.