Accession ID: MIRT002025 [miRNA, hsa-miR-124 :: CEBPA, target gene]
miRNA Infomation
miRNA namehsa-miR-124
miRNA-target interaction network
Gene Information
Gene Symbol CEBPA LinkOut: [ Entrez Gene | BioGPS | Wikipedia | iHop ]
Synonyms C/EBP-alpha, CEBP
Description CCAAT/enhancer binding protein (C/EBP), alpha
Transcript NM_004364   LinkOut: [ RefSeq ]
Expression LinkOut: [ BioGPS ]
KEGG Pathway hsa05200    Pathways in cancer - Homo sapiens (human)
hsa05221    Acute myeloid leukemia - Homo sapiens (human)
Putative miRNA Targets on CEBPA LinkOut: [ TargetScan 5.1 | MicroCosm | miRNAMap 2.0 ]
3'UTR of CEBPA
(miRNA target sites are highlighted)		 
>CEBPA|NM_004364|3'UTR
   1 TGAGGCGCGCGGCTGTGGGACCGCCCTGGGCCAGCCTCCGGCGGGGACCCAGGGAGTGGTTTGGGGTCGCCGGATCTCGA
  81 GGCTTGCCCGAGCCGTGCGAGCCAGGACTAGGAGATTCCGGTGCCTCCTGAAAGCCTGGCCTGCTCCGCGTGTCCCCTCC
 161 CTTCCTCTGCGCCGGACTTGGTGCGTCTAAGATGAGGGGGCCAGGCGGTGGCTTCTCCCTGCGAGGAGGGGAGAATTCTT
 241 GGGGCTGAGCTGGGAGCCCGGCAACTCTAGTATTTAGGATAACCTTGTGCCTTGGAAATGCAAACTCACCGCTCCAATGC
 321 CTACTGAGTAGGGGGAGCAAATCGTGCCTTGTCATTTTATTTGGAGGTTTCCTGCCTCCTTCCCGAGGCTACAGCAGACC
 401 CCCATGAGAGAAGGAGGGGAGCAGGCCCGTGGCAGGAGGAGGGCTCAGGGAGCTGAGATCCCGACAAGCCCGCCAGCCCC
 481 AGCCGCTCCTCCACGCCTGTCCTTAGAAAGGGGTGGAAACATAGGGACTTGGGGCTTGGAACCTAAGGTTGTTCCCCTAG
 561 TTCTACATGAAGGTGGAGGGTCTCTAGTTCCACGCCTCTCCCACCTCCCTCCGCACACACCCCACCCCAGCCTGCTATAG
 641 GCTGGGCTTCCCCTTGGGGCGGAACTCACTGCGATGGGGGTCACCAGGTGACCAGTGGGAGCCCCCACCCCGAGTCACAC
 721 CAGAAAGCTAGGTCGTGGGTCAGCTCTGAGGATGTATACCCCTGGTGGGAGAGGGAGACCTAGAGATCTGGCTGTGGGGC
 801 GGGCATGGGGGGTGAAGGGCCACTGGGACCCTCAGCCTTGTTTGTACTGTATGCCTTCAGCATTGCCTAGGAACACGAAG
 881 CACGATCAGTCCATCCCAGAGGGACCGGAGTTATGACAAGCTTTCCAAATATTTTGCTTTATCAGCCGATATCAACACTT
 961 GTATCTGGCCTCTGTGCCCCAGCAGTGCCTTGTGCAATGTGAATGTGCGCGTCTCTGCTAAACCACCATTTTATTTGGTT
1041 TTTGTTTTGTTTTGGTTTTGCTCGGATACTTGCCAAAATGAGACTCTCCGTCGGCAGCTGGGGGAAGGGTCTGAGACTCC
1121 CTTTCCTTTTGGTTTTGGGATTACTTTTGATCCTGGGGGACCAATGAGGTGAGGGGGGTTCTCCTTTGCCCTCAGCTTTC
1201 CCCAGCCCCTCCGGCCTGGGCTGCCCACAAGGCTTGTCCCCCAGAGGCCCTGGCTCCTGGTCGGGAAGGGAGGTGGCCTC
1281 CCGCCAACGCATCACTGGGGCTGGGAGCAGGGAAGGACGGCTTGGTTCTCTTCTTTTGGGGAGAACGTAGAGTCTCACTC
1361 TAGATGTTTTATGTATTATATCTATAATATAAACATATCAAAGTCAA
Target sites Provided by authors  Predicted by miRanda
Experimental Support 1 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-124 :: CEBPA    [ Functional MTI ]
Validation Method Microarray
Conditions HeLa
Location of target site 3'UTR
Original Description (Extracted from the article) ... Filtering the expression profiles for genes characterized by the LocusLink database12 that were significantly downregulated (P < 0.001) at both 12 and 24 h, gave sets of 96 and 174 annotated genes downregulated by miR-1 and miR-124, respectively (Supplementary Tables 1 and 2).//{These MTI shown in Supplementary Table 1,2,4} ...

- Lim, L. P. Lau, N. C. Garrett-Engele, P. et al., 2005, Nature.
miRNA-target interactions (Provided by authors)
IDDuplex structurePosition
1 
miRNA  3' ccguaaguggcgCACGGAau 5'
                      ||||||  
Target 5' ------------GUGCCU-- 3'
 		1 - 6
Article - Lim, L. P. Lau, N. C. Garrett-Engele, P. et al.
- Nature, 2005
MicroRNAs (miRNAs) are a class of noncoding RNAs that post-transcriptionally regulate gene expression in plants and animals. To investigate the influence of miRNAs on transcript levels, we transfected miRNAs into human cells and used microarrays to examine changes in the messenger RNA profile. Here we show that delivering miR-124 causes the expression profile to shift towards that of brain, the organ in which miR-124 is preferentially expressed, whereas delivering miR-1 shifts the profile towards that of muscle, where miR-1 is preferentially expressed. In each case, about 100 messages were downregulated after 12 h. The 3' untranslated regions of these messages had a significant propensity to pair to the 5' region of the miRNA, as expected if many of these messages are the direct targets of the miRNAs. Our results suggest that metazoan miRNAs can reduce the levels of many of their target transcripts, not just the amount of protein deriving from these transcripts. Moreover, miR-1 and miR-124, and presumably other tissue-specific miRNAs, seem to downregulate a far greater number of targets than previously appreciated, thereby helping to define tissue-specific gene expression in humans.
LinkOut: [PMID: 15685193]
Experimental Support 2 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-124 :: CEBPA    [ Functional MTI ]
Validation Method Luciferase reporter assay , Western blot , Reporter assay
Conditions K562,
Location of target site 3'UTR
Tools used in this research TargetScan,
Original Description (Extracted from the article) ... Using a computational microRNA (miRNA) prediction approach and functional studies, we show that C/EBPa mRNA is a target for miRNA-124a. This miRNA is frequently silenced by epigenetic mechanisms in leukemia cell lines, becomes up-regulated after epigenetic treatment, and targets the C/EBPa 3ΒΆ untranslated region. ...

- Hackanson, B. Bennett, K. L. Brena, R. M. et al., 2008, Cancer Res.
Article - Hackanson, B. Bennett, K. L. Brena, R. M. et al.
- Cancer Res, 2008
Functional loss of CCAAT/enhancer binding protein alpha (C/EBP alpha), a master regulatory transcription factor in the hematopoietic system, can result in a differentiation block in granulopoiesis and thus contribute to leukemic transformation. Here, we show the effect of epigenetic aberrations in regulating C/EBP alpha expression in acute myeloid leukemia (AML). Comprehensive DNA methylation analyses of the CpG island of C/EBP alpha identified a densely methylated upstream promoter region in 51% of AML patients. Aberrant DNA methylation was strongly associated with two generally prognostically favorable cytogenetic subgroups: inv(16) and t(15;17). Surprisingly, while epigenetic treatment increased C/EBP alpha mRNA levels in vitro, C/EBP alpha protein levels decreased. Using a computational microRNA (miRNA) prediction approach and functional studies, we show that C/EBP alpha mRNA is a target for miRNA-124a. This miRNA is frequently silenced by epigenetic mechanisms in leukemia cell lines, becomes up-regulated after epigenetic treatment, and targets the C/EBP alpha 3' untranslated region. In this way, C/EBP alpha protein expression is reduced in a posttranscriptional manner. Our results indicate that epigenetic alterations of C/EBP alpha are a frequent event in AML and that epigenetic treatment can result in down-regulation of a key hematopoietic transcription factor.
LinkOut: [PMID: 18451139]