Selenium and cell proliferation inhibition in breast cancer: the role of the micronutrient on prolactin pathway focusing on miR-106b and its target p21

• Grant number: 22/14752-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2023
• End date: January 31, 2024
• Field of knowledge: Health Sciences - Nutrition - Nutrition Biochemistry
• Principal Investigator: Thomas Prates Ong
• Grantee: Hellen Messias Silva
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 13/07914-8 - FoRC - Food Research Center, AP.CEPID

Abstract

Breast cancer is a multifactorial disease, in which risk factors such as eating habits, exercise, sex, age and genetic factors are associated with the tumor. It is a hormone-dependent disease, in which estrogen stands out, whose direct actions increase the risk for the development of breast cancer. Although estrogen is the main hormone studied in this area, currently interest has also been focused on the effect of the prolactin pathway on breast tumorigenesis. Studies show that high levels of prolactin are linked to breast cancer. More specifically, increased expression of prolactin receptors is observed in MCF-7 human breast cancer cells. Furthermore, prolactin inhibits the expression of p21, a regulator of cell division, through upregulation of MicroRNA-106b-5p that targets p21. Among the food components with an anti-breast cancer effect, the micronutrient selenium stands out. Its antioxidant capacity and inhibition of cell proliferation make it a fundamental component of the diet for protection against mammary tumors. Furthermore, a previous study by our group showed the ability to inhibit proliferation and epigenetic modulation by selenium in MCF-7 cells (DE MIRANDA et al., 2014). Although the anti-breast cancer activities of selenium have been related to different mechanisms, including the level of DNA methylation and histone modifications, it is not yet known whether protective actions would involve hormonal modulation, specifically of the prolactin pathway. Thus, the present scientific initiation project seeks to elucidate whether the inhibitory actions of selenium on cell proliferation in MCF-7 cells, previously observed (DE MIRANDA et al., 2014), would involve actions of the micronutrient in the prolactin pathway, as inhibition of its receptor expression and/or through miR-106b and its p21 target.