Functional study of the modulation of microRNAs, miR-451 and miR-720, in human tumor cell lines

• Grant number: 12/23326-6
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2013
• End date: November 30, 2015
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Daniel Onofre Vidal
• Grantee: Daniel Onofre Vidal
• Host Institution: Hospital do Câncer de Barretos. Fundação Pio XII (FP). Barretos , SP, Brazil
• Associated researchers: André Lopes Carvalho ; Rui Manuel Vieira Reis

Abstract

microRNAs (miRNAs) comprise a class of non-coding RNAs (ncRNAs) that are involved in the regulation of gene expression. Experimental evidences support that miRNAs may act as inhibitors of the translation process, or to promote protein degradation or also in the target mRNA degradation. Although the mechanism is not fully elucidated, indeed miRNAs play important roles in a number of biological processes such as cell development, growth, proliferation, apoptosis and differentiation. Several reports have shown that miRNAs play a crucial role in the development of several diseases, including cancer. In recent findings, we observed that miR-451 and miR-720 demonstrated high expression in normal tissues samples relative to its expression in correspondent tumor cell lines. Moreover, the development of functional assays by overexpression of these miRNAs in cancer cell lines revealed the importance of these miRNAs in the control of the proliferation mechanism of these cells. Similar observations can be seen in miRNAs with tumor suppressor characteristics. For miR-451 this characteristic is already well established in the literature. On the other hand, for miR-720 the literature is controversial regarding its differential expression in different tumor types suggesting that its action is dependent upon the cellular context, in some tissues acting as a tumor promoter and in others as a tumor suppressor. Therefore, we propose in this project a comprehensive functional evaluation of miR-451 and miR-720 in human tumor cell lines. Functional assessment of these miRNAs and their target gene in these tumor cell lines may contribute to the understanding of the biology of the tumoral process. Moreover, since the modulation of miRNAs appears to be a promising strategy for cancer treatment, this study may contribute to the identification of new potential molecular targets for the establishment and direction of new therapeutic strategies to fight this disease. (AU)