Jéssica Zani Lacerda, Lívia Carvalho Ferreira, Beatriz Camargo Lopes, Andrés Felipe Aristizábal-Pachón, Marcio Chaim Bajgelman, Thaiz Ferraz Borin and Debora Aparecida Pires de Campos Zuccari* Pages 237 - 247 ( 11 )
Background: The high mortality rate of breast cancer is related to the occurrence of metastasis, a process that is promoted by tumor angiogenesis. MicroRNAs are small molecules of noncoding mRNA that play a key role in gene regulation and are directly involved in the progression and angiogenesis of various tumor types, including breast cancer. Several miRNAs have been described as promoters or suppressors angiogenesis and may be associated with tumor growth and metastasis. Melatonin is an oncostatic agent with a capacity of modifying the expression of innumerable genes and miRNAs related to cancer.
Objective: The aim of this study was to evaluate the role of melatonin and the tumor suppressor miR- 148a-3p on angiogenesis of breast cancer.
Method: MDA-MB-231 cells were treated with melatonin and modified with the overexpression of miR-148a-3p. The relative quantification in real-time of miR-148a-3p, IGF-IR and VEGF was performed by real-time PCR. The protein expression of these targets was performed by immunocytochemistry and immunohistochemistry. Survival, migration and invasion rates of tumor cells were evaluated. Finally, the xenograft model of breast cancer was performed to confirm the role of melatonin in the tumor.
Results: The melatonin was able to increase the gene level of miR-148a-3p and decreased the gene and protein expression of IGF-1R and VEGF, both in vitro and in vivo. In addition, it also had an inhibitory effect on the survival, migration and invasion of breast tumor cells.
Conclusion: Our results confirm the role of melatonin in the regulation of miR-148a-3p and decrease of angiogenic factors.
triple negative breast cancer, miRNA, pineal gland, angiogenic proteins, tumor cells, xenograft model.
Sao Paulo State University (Unesp), Institute of Biosciences, Humanities and Exact Sciences (Ibilce), Sao Jose do Rio Preto (SP), Laboratory of Molecular Research in Cancer (LIMC), Medical School of Sao Jose do Rio Preto (FAMERP), Sao Jose do Rio Preto (SP), Sao Paulo State University (Unesp), Institute of Biosciences, Humanities and Exact Sciences (Ibilce), Sao Jose do Rio Preto (SP), Laboratory of Molecular Genetics and Bioinformatics (LGMB), Faculty of Medicine of Ribeirao Preto, University of Sao Paulo (FMRP/USP), Ribeirao Preto (SP), Laboratory of Biosciences of the National Center of Research in Energy and Materials (LNBio/CNPEM), Campinas (SP), Augusta University, 1120 15th Street, Augusta, GA 30912, Sao Paulo State University (Unesp), Institute of Biosciences, Humanities and Exact Sciences (Ibilce), Sao Jose do Rio Preto (SP)