Effect of aerobic physical training on the expression of circulating and muscular myomiRs in experimental models of cancer

Author(s)

João Lucas Penteado Gomes

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Escola de Educação Física e Esportes (EEFE/BT)
• Defense date: 2017-09-25

Examining board members

Edilamar Menezes de Oliveira; Patricia Chakur Brum; Murilo Vieira Geraldo

• Advisor: Edilamar Menezes de Oliveira

Abstract

Cancer is the name designated for a set of more than 100 diseases. Cancer cells can be very aggressive, uncontrollable and with a high rate of cell division, so cancer has a progressive and degenerative nature and is a problem of global public health (INCA, 2017). There are several comorbidities associated with cancer that lead to higher mortality and worsening of the disease, one of which is cachexia. MicroRNAs are a class of molecules that has been highly investigated for being related to several physiological and also pathological factors (AMBROS, 2001). It is known that several microRNAs have altered expression in individuals with cancer. These changes in the expression of microRNAs are found in the bloodstream, tumor and in some tissues, such as skeletal and cardiac muscle. (CHEN et al., 2014). On the other hand, aerobic physical exercise causes profound skeletal adaptations, including in pathological conditions. One of the most striking is the normalization of the balance between synthesis and protein degradation in the skeletal myocyte (CUNHA et al, 2012). Aerobic physical exercise plays an important role in the regulation of the expression of several microRNAs. It has therapeutic potential to restore the expression of several altered microRNAs present in different diseases (FERNANDES et al., 2011). In our study we analyzed the expression of microRNAs enriched in skeletal muscle (myomiRs) using two models MMTV-PyMT (breast cancer, non-cachectic) and CT26 (colon cancer, cachectic). These animals were divided into sedentary and trained groups and controls were healthy animals also divided into sedentary and trained. We observed that MMTV animals showed no loss of function and muscle mass, however, two myomiRs, miR-206 and 486, have altered expression in skeletal muscle and circulation as a function of cancer, and physical exercise does not influence their expression. We also evaluated the same parameters in the CT26 model; The expression of myomiRs-206 and 486 is also altered in the circulation and skeletal muscle, and physical exercise does not influence the expression of these microRNAs. In this model the expression of PI3K protein is decreased and PTEN is increased as a function of cancer. Our results indicate that microRNAs 206 and 486 have altered expression in muscle tissue and circulation due to cancer, independent of cachexia, and may be markers of damage in the pathways of protein synthesis in muscle tissue (AU)

• FAPESP's process: 15/04788-7 - Effects of aerobic physical training on blood circulation and skeletal muscle myomiRs expression in a experimental breast cancer model
• Grantee: João Lucas Penteado Gomes
• Support Opportunities: Scholarships in Brazil - Master