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

Researchers at the University of Genoa aimed to explore the involvement of miRNAs in beneficial effects exerted by physical activity in breast cancer prevention.

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. The different expressions of two miRNAs involved in breast cancer progression, i. e. up-regulation of mi R-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. The evaluation of these miRNAs in the blood can be used as non-invasive biomarkers for breast cancer prevention.

Dr. Alessandra Pulliero from the Department of Health Sciences at The University of Genoa said, “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.”

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 cancer relapse and improving their immune functions. Structured exercise improves insulin resistance, reduces hyperinsulinaemia and reduces the risk for diabetes, which could explain the link between increased structured exercise and reduced risk for these cancers.


(A) Scatter plot reporting variations of miRNA expression before and after physical activity as evaluated by microarray in 30 subjects testing 1,900 microRNAs in blood plasma. MiRNAs, whose expression was modified by physical activity, were identified as red dots in scatter-plot. (B) Up-modulation of miR-206 and down-modulation of miR-30c in transfected MCF7 cells (logarithmic scale). qPCR analysis of miR-206 and miR-30c expression after transfection of miR-206 mimics and miR-30c siRNA. The data were reported as variation in respect to their expression in the control. The fold change in the samples (MCF7 cells transfected with miRNA-mimic and/or siRNA) was normalized to the reference RNU6 and expressed relative to a calibrator sample (mock MCF7 sample) using the 2−(ΔΔCt ± SD) method.

Recent findings indicate that women with a history of breast cancer who engage in more than 9 metabolic equivalent h/week of structured exercise after a breast cancer diagnosis had a significantly lower risk of death or breast cancer recurrence than women who were physically inactive. Incubation of MCF-7 estrogen-responsive breast cancer cells and MDA-MB-231 triple-negative breast cancer cells treated with post-exercise serum, from both healthy volunteers and operated cancer patients resulted in a reduction of breast cancer cell viability in comparison with breast cancer cells incubated with pre-exercise sera. Accordingly, the authors analyzed circulating miRNAs expression profiles before and after structured exercise and evaluated their potential anti-cancer properties in breast cancer cells.

The researchers concluded “this study provides evidence that miRNA modulation is a specific molecular mechanism through which structured exercise exerts preventive effects against cancer. The possibility of using these two miRNAs for breast cancer prevention is of interest. MicroRNA as delivered by lipid nanoparticles has been already been effective in mice in preventing NNK induced lung cancer. However, insofar no similar experiments exist as far as concern breast cancer prevention. Moreover, the evaluation of miR-206 and anti-miR-30c levels in the blood of breast cancer patients could be useful as non-invasive biomarkers in guiding future strategies for cancer prevention.”

Source – Oncotarget

Alessandra P, Ming Y, Pradeep C, Barbara M, Cinzia D, Barbara B, Paolo D, Luigi M, Fabio G, Alberto I. (2020) Anticancer effect of physical activity is mediated by modulation of extracellular microRNA in blood. Oncotarget 11: 2106-2119. [article]

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