Melatonin and miRNAs in triple negative breast cancer

Abstract

Breast cancer is the most prevalent type of tumor among women. The stages of initiation, progression and tumor invasion are triggered by genetic changes in tumor cells, that also receive influence of inflammatory and angiogenic factors released in the tumor microenvironment. MicroRNAs (miRNAs) are small non-coding mRNA molecules that play an important role in gene regulation. Several miRNAs have been described as promoters or suppressors of inflammation, angiogenesis, and metastasis. Melatonin, a hormone secreted by the pineal gland, has shown oncostatic effects, and recently a study has shown that it can modulate the expression of miRNAs in breast cancer, promoting an anti-tumor action. The objective of this study is to evaluate, in an in vitro and in vivo studies, the action of melatonin in the expression of miRNAs that regulate inflammation, angiogenesis and metastasis in breast cancer. The differential expression of miRNAs will be evaluated by PCR-Array in triple negative breast cancer cell lines, treated or not with melatonin. The results will be submitted to the study of signaling pathways involved in tumor growth and metastasis processes and will be validated by overexpression or silencing of these miRNAs in an in vitro study and in models of primary breast tumors and metastases, treated or not with melatonin. The knowledge of miRNAs target involved in tumor progression and metastasis is extremely important because allows the use of these miRNAs of interest, overexpressed or inhibited, as therapeutic agents in synergy with melatonin in patients with breast cancer and also, enable the use of these markers as diagnostic or prognostic. (AU)