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Analysis of the expression profile of microRNAs and their target genes in human placenta for the identification of new tumor markers

Grant number: 10/08290-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): November 01, 2010
Effective date (End): February 29, 2012
Field of knowledge:Biological Sciences - Genetics
Principal Investigator:Wilson Araújo da Silva Junior
Grantee:Daniel Onofre Vidal
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The human placenta is a highly specialized embryonic tissue derived from the chorion, which together with the fetal membranes and amniotic fluid, supports the normal development of the embryo and fetus. The placenta has a specialized group of epithelial cells (trophoblasts) characterized by the ability to proliferate and invade the myometrium, providing the attachment of the embryo in the uterus. These characteristics resemble the molecular mechanisms that tumor cells use during tumorigenesis. This observation suggests that both the placenta and tumor cells share the same genetic program to exert its function. Another property that both cells have in common is the ability to escape from the action of the immune system, therefore, presenting immunological tolerance. The difference lies in the fact that such mechanisms in the placenta are tightly regulated, whereas in tumors these processes are stochastic. A series of genes involved in regulation of proliferation and invasion of the placenta may be regulated by microRNAs (miRNAs). miRNAs are small non coding RNA molecules that have the ability to modulate gene expression of approximately 30% of mammalian genes associated with various biological processes such as proliferation, invasion, cell adhesion, metastasis, among others. In the placenta, miRNAs must also play a role in regulating such biological processes, especially those involved in the development of the placenta. Since trophoblasts share molecular mechanisms inherent to tumor development, the placenta becomes an ideal model of study to identify new genes or gene pathways involved in tumorigenesis. miRNAs that present high expression in placenta and in different types of cancer, but with relatively restricted expression in normal tissues are potential targets for the development of new therapeutic approaches against cancer. Therefore, we propose to evaluate the global expression of miRNAs and their target genes in human placenta from the third trimester of pregnancy, with the aim of identifying new tumor markers. (AU)