Identification of Modulated MicroRNAs Associated with Breast Cancer, Diet, and Physical Activity

SIMPLE SUMMARY: Healthy diet and physical activity are able to induce beneficial molecular modifications that have been associated with a lower risk of breast cancer (BC) incidence and a better prognosis for BC patients. Although the beneficial effects of healthy lifestyle have been described, the beneficial epigenetic modifications induced by dietary and exercise intervention in BC patients have not been elucidated yet. On these bases, the aim of the present study was to computationally identify microRNAs (miRNAs) strictly associated with BC progression and with dietary and exercise interventions. Through several computational approaches, a set of miRNAs modulated by diet and exercise and useful as diagnostic and prognostic biomarkers for BC was identified. The results obtained represent the starting point for further validation analyses performed on BC patients undergoing lifestyle interventions to propose the miRNAs here identified as novel biomarkers for BC management. ABSTRACT: Background: Several studies have shown that healthy lifestyles prevent the risk of breast cancer (BC) and are associated with better prognosis. It was hypothesized that lifestyle strategies induce microRNA (miRNA) modulation that, in turn, may lead to important epigenetic modifications. The identification of miRNAs associated with BC, diet, and physical activity may give further insights into the role played by lifestyle interventions and their efficacy for BC patients. To predict which miRNAs may be modulated by diet and physical activity in BC patients, the analyses of different miRNA expression datasets were performed. Methods: The GEO DataSets database was used to select miRNA expression datasets related to BC patients, dietary interventions, and physical exercise. Further bioinformatic approaches were used to establish the value of selected miRNAs in BC development and prognosis. Results: The analysis of datasets allowed the selection of modulated miRNAs associated with BC development, diet, and physical exercise. Seven miRNAs were also associated with the overall survival of BC patients. Conclusions: The identified miRNAs may play a role in the development of BC and may have a prognostic value in patients treated with integrative interventions including diet and physical activity. Validation of such modulated miRNAs on BC patients undergoing lifestyle strategies will be mandatory.