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

Egidio Celentano,Massimo Libra,Maria Grimaldi,Livia S. A. Augustin,Luca Falzone

doi:10.3390/cancers12092555

Egidio Celentano, Massimo Libra

Open Access

https://doi.org/10.3390/cancers12092555

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Abstract

Simple SummaryHealthy 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.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.

Highlights

Breast cancer (BC) represents the second most diagnosed cancer worldwide and the leading cause of cancer death in women accounting, respectively, for 2,088,849 million new diagnoses and over625,000 deaths annually [1]
We proposed the integrated analysis of different miRNA expression profiling datasets obtained from the GEO DataSets related to breast cancer (BC) patients with dietary or exercise interventions
The integration of different miRNA expression microarray datasets and the use of several bioinformatics prediction tools has allowed for the identification of miRNAs strictly involved in BC

Summary

Introduction

Breast cancer (BC) represents the second most diagnosed cancer worldwide and the leading cause of cancer death in women accounting, respectively, for 2,088,849 million new diagnoses and over625,000 deaths annually [1]. Adopted integrative therapies for BC patients include nutraceutical products like vitamins, flavonoids and natural extracts [8,9], prebiotics and probiotics [10,11], the adoption of a healthy lifestyle mainly represented by moderate or intense physical exercise [12,13], and the adherence to healthy or hypocaloric diets [5,14] Such approaches have been adopted following the association of cancer development with the dysbiosis of human microbiota, unhealthy lifestyle habits, hypercaloric diets, hormonal imbalances, and metabolic disorders [15,16,17,18,19]. Validation of such modulated miRNAs on BC patients undergoing lifestyle strategies will be mandatory

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