MicroRNAs expression in acute promyelocitic leukemia upon ATRA treatment

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MicroRNAs are small non-protein coding RNAs of 19 to 25 nucleotides that regulates gene expression targeting messenger RNAs (mRNA) in a sequence specific manner inducing translational repression or mRNA degradation depending on the degree of complementarity between miRNAs and their targets . For the few microRNAs whose function is known, they play important roles in development, differentiation, metabolism, cell growth and death in animals and plants. Recently microRNAs have been described to be involved in the regulation of mice hematopoiesis and to be disregulated in chronic lymphocytic leukemias and other lymphoproliferative disorders of B origin. However little is known about miRNAs are regulated and their role in myelopoiesis. Acute Promyelocytic leukemia (APL) is a subtype of acute myelogenous leukemia, which results from the translocation of the promyelocytic gene (PML) gene in the chromosme 15 and the retinoic acid receptotr alpha gene ( RARa) in chromosome 17. . This traslocation creates a novel oncogenic fusion protein which induces maturation arrest at the promyelocytic stage of granulocytic diffrentiation Pharmacological dosis of all-trans-retinoic acid (ATRA) reverse the dominant negative effect of the oncogenic protein fusion PML-RARa and induce differentiation of APL cells in vitro and in vivo . Indeed this is one of the best studied cell models of differentiation. In the present study, we analyze the microRNAs expression in APL cell lines upon ATRA treatment using microRNAs microarrays. Among the up-regulated microRNAs upon ATRA treatment, three microRNAs are predicted to target the same gene, which is a recently discover hematopoietic transcription factor involved in myeloid differentiation. Furthermore we identified and validated several other microRNA targets, which are genes activated by ATRA and involved in retinoic acid signaling. Thus, ATRA simultaneously induced retinoic acid signaling genes and modulate their expression throught a microRNA based mechanism.