MicroRNA miR-181a correlates with morphological sub-class of acute myeloid leukaemia and the expression of its target genes in global genome-wide analysis

Abstract

MicroRNAs (miRNAs) are short single-stranded RNAs that have a potentially important role in gene regulation. Using a quantitative real-time polymerase chain reaction assay specific to the mature miRNA, the expression level of a selected group of haematopoietic tissue-specific miRNAs was measured across a set of 30 primary adult acute myeloid leukaemia (AML) with a normal karyotype. The expression levels of each miRNA were correlated with the genome-wide mRNA expression profiles in the same leukaemias. This revealed that miR181a correlated strongly with the AML morphological sub-type and with the expression of genes previously identified through sequence analysis as potential interaction targets. Three other miRNAs, miR-10a, miR-10b and miR-196a-1, showed a clear correlation with HOX gene expression. Leukemia (2007) 21, 912-916.

MicroRNA-196a targets annexin A1: a microRNA-mediated mechanism of annexin A1 downregulation in cancers

“…Our study has added ANXA1 mRNA as one more bonafide target of miR-196a, which has also been implicated in targeting HOXB8, HOXC8, HOXD8 and HOXA7 mRNAs (Yekta et al, 2004). A high degree of negative correlation found between miR-196a and HOX genes in acute myeloid leukemia provides further confirmation of its role in the regulation of HOX gene expression (Debernardi et al, 2007). The elevated expression of HOX genes in leukemogenesis is very well established (Thorsteinsdottir et al, 1997(Thorsteinsdottir et al, , 2002, and in that respect, as a negative regulator of HOX gene expression, miR-196a might be considered a potential tumor suppressor in leukemia.…”

Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder

“…It is of note that miR-155 may also be elevated in other subtypes of AML where we did not have enough samples to make such a conclusion. If miR-155 does prove to be dysregulated in specifi c subtypes of AML, it might complement the recent fi nding that miR-181 expression positively correlates with M1 and M2 subtypes of AML, but not M4 or M5 ( 22 ). Furthermore, as the full spectrum of miRNAs that become dysregulated during AML is defi ned, these small RNAs may prove to have utility as diagnostic indicators of AML subtypes.…”

MicroRNAs in acute leukemia: from biological players to clinical contributors

“…For example, miR-196b is co-expressed with its neighboring genes HOXA9 and HOXA10 in MLL-rearranged ALL, 57 T-ALL 57 and AML patients. 23 Similar co-activation may explain the high association for miR-10a (positioned in between HOXB4 and HOXB5) as well as miR-196a (encoded in between HOXB9 and HOXB13) with the HOXB cluster as observed in adult 25,71 and childhood AML. 23 It is, however, intriguing that aberrant expression of neighboring genes, genomic aberrations and specific regulatory factors can only explain the minority of dysregulated miRNAs whereas an explanation is still lacking for the majority of aberrantly expressed miRNAs in acute leukemia.…”