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

Recent evidence has shown that deregulated expression of members of the micro RNA ‐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...

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Published in:Cancer science 2015-10, Vol.106 (10), p.1264-1277
Main Authors: Oliveira, Lucila H., Schiavinato, Josiane L., Fráguas, Mariane S., Lucena‐Araujo, Antonio R., Haddad, Rodrigo, Araújo, Amélia G., Dalmazzo, Leandro F., Rego, Eduardo M., Covas, Dimas T., Zago, Marco A., Panepucci, Rodrigo A.
Format: Article
Language:English
Subjects:
Acute lymphoblastic leukemia
Antibiotics
Bone marrow
Cancer
Demethylation
Deoxyribonucleic acid
DNA
DNA methylation
DNA microarrays
Epigenetics
Experiments
Gene expression
Hematology
Leukemia
Lymphatic leukemia
Lymphocytes T
Mcl-1 protein
MicroRNAs
miRNA
Molting
Roles
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Summary:Recent evidence has shown that deregulated expression of members of the micro RNA ‐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 ( CDK 6, PXDN , MCL 1, PIK 3R1, and CXXC 6), including targets with roles in active and passive DNA demethylation (such as DNMT 3a, DNMT 3b, 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.
ISSN:1347-9032
1349-7006
DOI:10.1111/cas.12766