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In vivo analysis of the oncogenes MYC and KRAS expression in metastasis of prostate cancer from mice treated with miR-145

Grant number: 15/22250-4
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): February 01, 2016
Effective date (End): January 31, 2017
Field of knowledge:Health Sciences - Medicine - Surgery
Principal Investigator:Kátia Ramos Moreira Leite
Grantee:Pedro Averbach
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Despite the great advances in available treatments for prostate cancer, this condition remains a major health issue, with an alarming incidence and mortality. The increasing knowledge of its molecular characteristics opens allows the development of new therapies that target specific molecules related to the pathogenesis of this disease. The role of microRNAs - not coding small strands of RNA involved in post-transcriptional control of various genes - has been studied, and changes in the expression pattern of these molecules is related to tumor development and progression. Within prostate cancer, the miR-145 stands out as its subexpression correlates with biochemical recurrence of the tumor and development of metastasis. Some studies attribute to miR-145 the control of the expression of cMyc and Kras oncogene, although it stills not clear whether the intravenous administration of miR-145 in vivo models significantly reduces the expression of these oncogenes. For this purpose, we will induce the appearance of prostate cancer metastases in nude mice by intraventricular injection of tumor cells. We will further split those mice into two groups, one being a negative control and another that will undergo intravenous administration of miR-145. After euthanasia of animals, we will carry out the analysis of the expression of cMyc and Kras oncogene by RT-PCR method of the affected tissues. Then we will compare the expression patterns in both groups in order to evaluate the effectiveness of intravenous administration of miR-145 in controlling the expression of oncogenes and cMyc and Kras.