Anticancer effect of physical activity is mediated by modulation of extracellular microRNA in blood
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Alessandra Pulliero1, Ming You2, Pradeep Chaluvally-Raghavan2,3, Barbara Marengo4, Cinzia Domenicotti4, Barbara Banelli5, Paolo Degan5, Luigi Molfetta6, Fabio Gianiorio7 and Alberto Izzotti4,5
1 Department of Health Sciences, University of Genoa, Genoa, Italy
2 Center for Disease Prevention Research, Medical College of Wisconsin, Milwaukee, WI, US
3 Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI, US
4 Department of Experimental Medicine, University of Genoa, Genoa, Italy
5 IRCCS Ospedale Policlinico San Martino, Genoa, Italy
6 Orthopaedics-Rehabilitation Unit, Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal-Infantile Sciences, University of Genoa, Genoa, Italy
7 Department of Internal Medicine, University of Genoa, Genoa, Italy
Keywords: circulating microRNAs; sports and exercise; carcinogenesis; cancer prevention; microRNA transfection
Received: February 27, 2020 Accepted: May 01, 2020 Published: June 02, 2020
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.
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