Identification of miRNA candidate and its target gene, modulated by melatonin and involved on angiogenesis in triple negative breast cancer

• Grant number: 16/14280-3
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2017
• End date: February 28, 2018
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Debora Aparecida Pires de Campos Zuccari
• Grantee: Jéssica Helena de Mora Marques
• Host Institution: Faculdade de Medicina de São José do Rio Preto (FAMERP). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São José do Rio Preto , SP, Brazil

Abstract

Breast cancer, the most common cancer among women, has as main cause of death tumor progression and metastatic spread that occur with the encouragement ofangiogenesis. MicroRNAs (miRNAs), small mRNA molecules noncoding that play a key role in gene regulation, have been widely studied and has demonstrated involvement in the initiation and progression of various tumors, including breast cancer. Several miRNAs are described as promoters or suppressors of angiogenesis,It may be associated with tumor growth and metastasis. Melatonin, the hormone secretedby the pineal gland, is proving a potential treatment for breast cancer present oncostáticos and antiangiogenic effects. The objective of this study is to evaluate the potential of melatonin action in controlling angiogenesis modulated by miRNAs in breast cancer, in an in vitro study. First the differential expression of miRNAs associated with angiogenesis process will be analyzed by PCR-array in umoral line MDA-MB-468 treated or not with melatonin, followed by in silico selection of a candidate miRNA and its potential target gene. The results are validated with overexpression or silencing of the study miRNA in two lines, MDA-MB-468 and MDA-MB-231 and subsequent verification of gene expression by real time PCR and protein by immunocytochemistry. The results achieved may identify miRNAs modulated candidatesby melatonin and involved in the formation of tumor blood vessels and thereby enable the establishment of potential therapeutic protocols for control of this mobile event, crucial for a worse prognosis in patients with breast cancer. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MARQUES, JESSICA H. M.; MOTA, ANDRE L.; OLIVEIRA, JESSICA G.; LACERDA, JESSICA Z.; STEFANI, JULIA P.; FERREIRA, LIVIA C.; CASTRO, TIALFI B.; ARISTIZABAL-PACHON, ANDRES F.; ZUCCARI, DEBORA A. P. C.. Melatonin restrains angiogenic factors in triple-negative breast cancer by targeting miR-152-3p: In vivo and in vitro studies. Life Sciences, v. 208, p. 131-138, SEP 1 2018. (16/14280-3, 15/04780-6)