Estudo do metabolismo de microRNAs na resistência de células leucêmicas / Study of microRNA metabolism in leukemik cells resistance

AUTOR(ES)
FONTE

IBICT - Instituto Brasileiro de Informação em Ciência e Tecnologia

DATA DE PUBLICAÇÃO

11/07/2011

RESUMO

Drug resistance is one of the main obstacles in cancer therapy. Frequently, the treatment of chronic myelogenous leukemia (CML) becomes inefficient due to the emergence of a resistant population of cancer cells. Therefore, comparative studies of resistant and non-resistant CML cell lines is extremely important to the understanding of molecular mechanisms involved in the acquisition of resistance and also to the evolution of new therapeutic protocols. A growing number of evidence supports an important role for microRNAs in carcinogenesis and tumoral aggressiveness. This study aims to better understand the role of microRNAs and their biosynthetic pathway in the phenotype of multi-drug resistance (MDR) of CML cells. To this purpose we worked with the leukemic cell lines K562 (non-resistant) and Lucena (MDR phenotype). The results obtained revealed that Lucena expresses high levels of Dicer endonuclease and intensely regulates microRNAs let-7a and miR-145 when compared to K562. Also, Dicer silencing in MDR cells enhanced sensitivity to the chemotherapic drug vincristine. Experiments with different cells lines showed that resistance to cisplatin and doxorubicin are correlated to Dicer expression levels. In CML cell lines, the identification of Dicer ligands points to the possibility of alternative roles for this endonuclease in the MDR phenotype. Among the newly found interactors in the resistant cell line are proteins involved in antioxidant defense, proliferation and metabolism of fatty acids and steroids. Accordingly, proteome data from K562 and Lucena cells emphasizes the importance of lipid metabolism and structural remodeling to the resistant phenotype. Overall, our data contributes to the understanding of the role played by microRNAs and Dicer in the complex and multifactorial MDR phenotype.

ASSUNTO(S)

leucemia cancer micrornas imunidade celular enzima dicer leukemia cancer micrornas cellular immunity dicer enzyme resistance

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