Anticancer effect of physical activity is mediated by modulation of extracellular microRNA in blood

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 downregulation 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.

Physical Activity as a Preventive Lifestyle Intervention Acts Through Specific Exosomal miRNA Species—Evidence From Human Short- and Long-Term Pilot Studies

“…Exercise was shown to modulate the expression of several miRNA species that in turn are protective against cancer ( Li et al, 2020 ; Pulliero et al, 2020 ). In our report we demonstrate this modulation observed after both short-term (0.5 year) and long-term (25 + years) regular exercise since our miR-23a, 451a, 223-3p, and miR-150-5p were all suppressed emphasizing the role of exercise in the prevention of several cancer entities.…”

“…In our report we demonstrate this modulation observed after both short-term (0.5 year) and long-term (25 + years) regular exercise since our miR-23a, 451a, 223-3p, and miR-150-5p were all suppressed emphasizing the role of exercise in the prevention of several cancer entities. Nevertheless, data on exercise-derived exosomal miRNA species in modulating cancer prevention is still in its infancy ( Pulliero et al, 2020 ). Therefore, elaborate research effort is required to reveal the role of exosomal miRNA species in this particular field.…”

Exercise-Induced Circulating microRNAs: Potential Key Factors in the Control of Breast Cancer

“…Thus, it has been suggested that this miRNA can translocate from skeletal muscle to circulation and to cancer cells, where it acts as an exercise-induced systemic factor downregulating tumor progression. Moreover, Pulliero, You ( Pulliero et al, 2020 ) showed that an exercise bout modulates the expression of 14 c-miRNAs involved in pathways relevant to the control of cancer development and progression (e.g., oncogene and metastasis suppression, cell proliferation, apoptosis, cancer invasion) in healthy postmenopausal women (54–78 years old). Specifically, c-miR-206 and c-miR-30c expression were upregulated and downregulated, respectively.…”

Extracellular Vesicles and Their Role in the Spatial and Temporal Expansion of Tumor–Immune Interactions

“…Apart from proteins, other factors like miRNA or metabolites, incorporated in EVs, are likely to play a role. It has been reported that several circulating miRNAs may mediate the beneficial effects of physical activity [91][92][93][94]. Amongst them, miR-206 was found to reduce breast cancer cell growth by slowing G1/S transition and inducing apoptosis in vitro.…”

“…Amongst them, miR-206 was found to reduce breast cancer cell growth by slowing G1/S transition and inducing apoptosis in vitro. Myoblasts that were stimulated by gravity to simulate physical activity were shown to release miRNA-microvesicles containing miR-206 [91]. Others have found miR-206 to be associated with the modulation of inflammation [95] and the promotion of antiangiogenic effects in exercising breast cancer patients [96].…”