Abstract 4446: Molecular profiling and threshold expression of microRNAs in mammary tissue of asymptomatic women

Abstract

Abstract Night shift-work and circadian dysfunction have been linked to increased incidence of breast cancer. Circadian modulation of gene expression is often mediated by microRNAs (miRNAs), small 18-25 nucleotide noncoding RNA molecules that regulate posttranscriptional gene expression via mRNA inactivation. Although miRNA dysregulation has been implicated in breast cancer development, the relationship between breast cancer incidence in women exposed to chronic circadian disruption and their miRNA profiles has not been examined due to the lack of existing normal profiles of expression. We first identified miRNA expressed in asymptomatic breast tissue and defined their baseline profiles in women exposed to a regular work schedule compared to those who experienced chronic circadian disruption by night shift work. Normal mammary tissue was obtained from women undergoing therapeutic breast reductions. Clinical metadata on work, stress, sleep, pregnancy, medical, medication, family, and surgical history were obtained through survey and chart review. We selected night shift work starting from 0700 to 0300 as a marker of circadian disruption. Our studies focused on two major comparisons. First, we determined qualitative oscillatory differences in miRNA variants expressed during day and night. Second, we determined statistically significant expression levels of those day and night miRNAs in shift workers. Mammary miRNA reads were mapped against the reference human genome and mature miRNA set. One-way ANOVA was used to compare miRNA expression levels between night shift and non-night shift workers, as well as miRNA expression between other clinical metadata. At present, twelve samples have undergone experimental and statistical analyses. Three out of the twelve samples were from night shift workers. One-way ANOVA was run on the top one hundred expressed miRNAs including hsa-miR-143-3p, hsa-miR-99a-5p, hsa-miR-21-5p, hsa-miR-10b-5p, and hsa-miR-148a-3p to exclude miRNAs with zero or extremely low counts. Analysis showed no significant difference in miRNA expression of normal samples between night shift and non-night-shift workers (p 0.06099), pregnant and nulliparous (p 0.2658), and women who breastfed and those who did not (p 0.111). There was significant difference in miRNA expression of normal samples between patients who had breast cancer in the opposite breast compared to those who did not (p 0.03269) and patients with sleep problems and those who did not (p 0.003448). It is interesting to note that night shift work and sleep problems both represent forms of circadian disruption, yet only the latter showed significant difference in miRNA expression between controls. It is expected that patients with cancer in the other breast may exhibit significantly different reads from patients who have never had breast cancer. Future analyses will be performed using additional samples to build on these findings. Citation Format: Andrew Y. Li, Kristin Knight, Margaret Kneifel, Mark Feldmann, Kurtis Moyer, Allan Dickerman, Carla Finkielstein. Molecular profiling and threshold expression of microRNAs in mammary tissue of asymptomatic women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4446. doi:10.1158/1538-7445.AM2017-4446