A novel oncogenic enhancer of estrogen receptor-positive breast cancer

Abstract

Estrogen receptor-positive (ER+) breast cancer accounts for the majority of breast cancers diagnosed, and nearly 20% of patients do not respond to endocrine therapy. The pathogenesis of ER+ breast cancer has not been well elucidated. The enhancer is a cis-regulatory element that promotes gene transcription and plays an important role in the spatiotemporal expression of cellular genes. Nevertheless, the oncogenic enhancer and its role in the occurrence and progression of cancer remain unclear. Here, we report a novel oncogenic enhancer (named αEmyc) for c-Myc and reveal its activation mechanism in ER+ breast cancer. The results demonstrated that αEmyc enhanced the transcription of downstream genes more than 20-fold. The deletion of the 7-bp region (GGTTGCA) in αEmyc significantly downregulated the expression of c-Myc, resulting in cell nuclear changes, cell-cycle arrest, cell apoptosis, and finally, remarkable inhibition of cell proliferation. In conclusion, the present study discovers a novel oncogenic enhancer αEmyc (801 base pairs [bp], at Chr8: 127668529–127669329) and offers a remarkable core enhancer target (GGTTGCA) of αEmyc for gene therapy of ER+ breast cancer.

Keywords

• MT: RNA/DNA Editing
• oncogenic enhancer αEmyc
• estrogen receptor-positive breast cancer
• gene therapy
• gene editing
• activation mechanism