Circular RNA regions differentially expressed following antihormonal exposure in the mouse mammary gland as candidate response biomarkers

Abstract

Antihormonal therapies such as selective oestrogen receptor modulators like tamoxifen or aromatase inhibitors like letrozole represent a cornerstone for breast cancer prevention and therapy of oestrogen receptor-positive breast cancer. Therapeutic monitoring can include blood tests and imaging; however, genetically-based approaches are not yet in practice. Ideally, a test would be able to detect a positive molecular response across different oestrogen pathway-suppressive approaches. Circular RNAs are a species of non-coding RNAs detectable in plasma that have been proposed as non-invasive therapeutic biomarkers. To determine whether a set of specific circular RNAs is altered across oestrogen-suppressive pathway approaches, we analysed mammary gland-specific total RNA sequencing data from two individual genetically engineered mouse models (GEMMs) of oestrogen pathway-induced breast cancer, with or without exposure to tamoxifen or letrozole. The nf-core/circrna pipeline was used to identify candidate circRNA regions that were differentially expressed in response to either tamoxifen or letrozole. We then screened for candidate circRNA regions that were differentially regulated by both antihormonals. Four up-regulated and 31 down-regulated candidate circRNA regions with host genes known to be expressed in human breast epithelial cells were identified as showing reproducible differential regulation in response to antihormonal treatment.