Effects of exercise training on microRNA regulation in colon cancer

Author(s)

Gabriel Cardial Tobias

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Escola de Educação Física e Esportes (EEFE/BT)
• Defense date: 2021-02-26

Examining board members

Edilamar Menezes de Oliveira; Roger Chammas; Marcelo Alves da Silva Mori; Carlos Ugrinowitsch

• Advisor: Edilamar Menezes de Oliveira

Abstract

Aerobic exercise reduces the incidence of several types of human cancer and decreases tumor growth and metastasis in different animal models. However, the mechanisms underlying these effects are not fully understood. MicroRNAs are often deregulated in colon tumors, and their dysregulation is associated with tumor progression and worse patient prognosis. However, it is unknown whether exercise training affects deregulated microRNAs decreasing tumor growth. Here, we observed that aerobic exercise training reduced CT26 and MC38 tumor growth, reduced CT26 exosomes uptake in distant pre-metastatic niches, reduced lung metastasis and increased animal survival. More importantly, exercise training also reduced tumor growth in immunodeficient NUDE mice. Both the tumor fragments and primary CT26 cells of the trained mice promoted less tumor growth. In addition, we found that exercise training reduced the systemic effects induced by the CT26 tumor, with the reduction of splenomegaly, attenuation of increased liver mass and attenuation of gastrocnemius mass loss. Mechanically, exercise training leads to a global decrease in the microRNA\'s expression in CT26 tumors. These results were accompanied by a reduction in the levels of Dicer and Xpo5 expression in tumors and in the CT26 cells. Finally, we found that lower levels of Dicer expression and, to a lesser extent, Xpo5 in colon tumors of patients are associated with longer patient survival (AU)

• FAPESP's process: 18/02351-9 - Role of microRNAs to the attenuation of the colon tumor growth induced by aerobic physical activity in mice
• Grantee: Gabriel Cardial Tobias
• Support Opportunities: Scholarships in Brazil - Doctorate