Abstract
Epidemiological studies provide evidence that physical activity reduces the risk of cancer, particularly of breast cancer. However, little is known about the underlying molecular mechanisms as related to microRNAs. The goal of the herein presented study is to explore the involvement of miRNAs in beneficial effects exerted by physical activity in breast cancer prevention. Thirty subjects (mean age: 57.1 ± 14.7 years) underwent 45 minutes of treadmill walking under standardized conditions. The levels of extracellular miRNAs were evaluated in blood plasma before and after structured exercise by means of microarray analysis of 1,900 miRNAs identifying mostly modulated miRNAs. Structured exercise has been found to modulate the expression of 14 miRNAs involved in pathways relevant to cancer. The different expression of two miRNAs involved in breast cancer progression, i. e. up-regulation of miR-206 and down-regulation of anti-miR-30c, were the most striking effects induced by exercise. The biological effects of these miRNAs were investigated in MCF-7 human breast cancer cells. miR-206 transfection and anti-miR-30c silencing, inhibited cell growth and increased apoptosis of MCF-7 cells. Moreover, the combined use of the two miRNAs further enhanced apoptosis and induced growth arrest in the G1/S phase of cell cycle. Our results support that physical activity effectively change the expression of extracellular miRNAs. Specifically, miR-206 up-regulation and anti-miR-30c down-regulation act as suppressors in breast cancer cells. The evaluation of these miRNAs in blood can be used as non-invasive biomarkers for breast cancer prevention.
Highlights
The relevance of structured exercise for public health has been addressed by the World Health Organization, and its lack is estimated to be the main risk factor for 21–25% of breast and colon cancer cases, 27% of diabetes cases, and 30% of ischemic heart disease cases [1, 2]
The regression line indicates that in trained physically active subjects (i. e. those having delta bpm below the 50th percentile) blood glucose was more markedly decreased than in untrained subjects having a sedentary lifestyle (P < 0.05), (Figure 1A). This finding indicates that training status is important in modulating the efficacy of structured exercise to induce a reduction of blood glucose levels
Among the most evident systemic effects found in the subjects analyzed in our study, a reduction of blood glucose levels has been reported after structured exercise
Summary
The relevance of structured exercise for public health has been addressed by the World Health Organization, and its lack is estimated to be the main risk factor for 21–25% of breast and colon cancer cases, 27% of diabetes cases, and 30% of ischemic heart disease cases [1, 2]. Several epidemiological studies demonstrated the dose-dependent protective effect of regular and moderate structured exercise against chronic degenerative diseases, www.oncotarget.com with a particular reference to both the primary (prevention of cancer onset) and tertiary (prevention of cancer relapses) prevention of cancer [2]. These findings refer only to structured physical activities, i. Breast cancer survivors engaging in structured exercise increase the drainage of lymph from their upper limbs, thereby decreasing the side effects of mastectomy, significantly lowering their risk of a cancer relapse and improving their immune functions [4]. Moderateintensity aerobic exercise combined with resistance training benefited early adjuvant breast cancer treatment; after 18 weeks of an exercise program, there was a positive effect on physical fatigue, cardiopulmonary function, and muscle strength among participating patients [6]
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