Potential roles of microRNA‐29a in the molecular pathophysiology of T‐cell acute lymphoblastic leukemia

Cancer Science

Lucila H. Oliveira³  Josiane L. Schiavinato⁴  Mariane S. Fráguas³  Antonio R. Lucena-Araujo¹  Rodrigo Haddad²  Amélia G. Araújo³  Leandro F. Dalmazzo³  Eduardo M. Rego³  Dimas T. Covas³  Marco A. Zago³ 

[1] Department of Genetics, Federal University of Pernambuco, Recife, Brazil;School of Ceilandia, University of Brasilia, Brasilia, Brazil;Department of Internal Medicine, Medical School of Ribeirão Preto, University of São Paulo, São Paulo, Brazil;Department of Genetics, Medical School of Ribeirão Preto, University of São Paulo, São Paulo, Brazil

关键词: DNMT;    epigenetic regulation;    miR‐29a;    T‐cell acute lymphoblastic leukemia;    TET;   

DOI  :  10.1111/cas.12766

来源: Wiley

【 摘 要 】

Abstract

Recent evidence has shown that deregulated expression of members of the microRNA-29 (miR-29) family may play a critical role in human cancer, including hematological malignancies. However, the roles of miR-29 in the molecular pathophysiology of T-cell acute lymphoblastic leukemia (T-ALL) has not been investigated. Here, we show that lower levels of miR-29a were significantly associated with higher blast counts in the bone marrow and with increased disease-free survival in T-ALL patients. Furthermore, miR-29a levels are extremely reduced in T-ALL cells compared to normal T cells. Microarray analysis following introduction of synthetic miR-29a mimics into Jurkat cells revealed the downregulation of several predicted targets (CDK6, PXDN, MCL1, PIK3R1, and CXXC6), including targets with roles in active and passive DNA demethylation (such as DNMT3a, DNMT3b, and members of the TET family and TDG). Restoring miR-29a levels in Jurkat and Molt-4 T-ALL cells led to the demethylation of many genes commonly methylated in T-ALL. Overall, our results suggest that reduced miR-29a levels may contribute to the altered epigenetic status of T-ALL, highlighting its relevance in the physiopathology of this disease.

【 授权许可】

CC BY-NC-ND   
© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

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