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Regulatory acction of melatonin on miR-17 and ROCK-1 in breast cancer metastatization

Grant number: 13/24975-0
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): April 01, 2014
Effective date (End): April 30, 2015
Field of knowledge:Agronomical Sciences - Veterinary Medicine
Principal Investigator:Debora Aparecida Pires de Campos Zuccari
Grantee:Rodrigo Inácio Pongeluppi
Home 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
Associated scholarship(s):14/22245-8 - Regulatory action of melatonin on miR-17 and ROCK-1 in breast cancer metastatization, BE.EP.IC

Abstract

Breast cancer is the most common neoplasia in women and have been frequently associated to high morbidities and mortalities rates, with great financial impact on heath systems. Besides, the disease is characterized by the high rates of metastasis, which worsen significantly the prognosis. This process is associated with two regulatory molecules, microRNAs (miRNAs), specially miR-17, and ROCK-1, which overexpressions have been associated to tumor growth and metastasis. In contrast, melatonin has shown oncostatics and antimetastasis properties by reducing the cell ability to migrate and invade the tissue, besides the inhibition of cell proliferation. Thus, the objective of this study is to determine the effect of melatonin on miR-17, and its target gene, ROCK-1, evaluating metastasis regulation by molecular and genetic expression of ROCK-1 and the genetic expression of miR-17 after melatonin treatment in metastatic breast cancer cells line, MDA-MB-231. The molecular expression of miR-17 will be verified by real time PCR and ROCK-1 molecular and proteic expressions will be evaluated by real time PCR and imunocitochemistry, respectively. Besides, an analisis of the ability of invasion and migration will be held by chamber Boyden assays to verify the inhibitory effect of those molecules. The results will determine the therapeutic value of melatonin on metastasis, contributing to compose potential therapeutic protocols for the control of this celular event, which is a determinant prognostic factor for the breast cancer patient.