Assessing the miRNA sponge potential of RUNX1T1 in t(8;21) acute myeloid leukemia.
t(8;21) acute myeloid leukemia (AML) is characterized by a translocation between chromosomes 8 and 21 and formation of a distinctive RUNX1-RUNX1T1 fusion transcript. This translocation places RUNX1T1 under control of the RUNX1 promoter leading to a pronounced upregulation of RUNX1T1 transcripts in t(8;21) AML, compared to normal hematopoietic cells. We investigated the role of highly-upregulated RUNX1T1 under the hypothesis that it acts as competing endogenous RNA (ceRNA) titrating microRNAs (miRNAs) away from their target transcripts and thus contributes to AML formation. Using publicly available t(8;21) AML RNA-Seq and miRNA-Seq data available from The Cancer Genome Atlas (TCGA) project, we obtained a network consisting of 605 genes that may act as ceRNAs competing for miRNAs with the suggested RUNX1T1 miRNA sponge. Among the 605 ceRNA candidates, 121 have previously been implied in cancer development. Players in the integrin, cadherin, and Wnt signaling pathways affected by the RUNX1T1 sponge were overrepresented. Finally, among a set of 21 high interest RUNX1T1 ceRNAs we found multiple genes that have previously been linked to AML formation. In conclusion, our study offers a novel look at the role of the RUNX1-RUNX1T1 fusion transcript in t(8;21) AML beyond previously investigated genetic and epigenetic aberrations.
Center for Non-coding RNA in Technology and Health, University of Copenhagen, Denmark; Department of Veterinary and Animal Sciences, University of Copenhagen, Denmark.
Alexander
A
Junge
The Granulocyte Research Laboratory, Department of Hematology, National University Hospital, University of Copenhagen, Copenhagen, Denmark.
Roza
R
Zandi
Center for Non-coding RNA in Technology and Health, University of Copenhagen, Denmark; Department of Veterinary and Animal Sciences, University of Copenhagen, Denmark.
Jakob Hull
JH
Havgaard
Center for Non-coding RNA in Technology and Health, University of Copenhagen, Denmark; Department of Veterinary and Animal Sciences, University of Copenhagen, Denmark. Electronic address: gorodkin@rth.dk.
Jan
J
Gorodkin
The Granulocyte Research Laboratory, Department of Hematology, National University Hospital, University of Copenhagen, Copenhagen, Denmark; Section of Haematology-Oncology, Department of Clinical Genetics, National University Hospital, University of Copenhagen, Copenhagen, Denmark. Electronic address: jack.cowland@regionh.dk.
Jack Bernard
JB
Cowland
D020413:3' Untranslated Regions; D001665:Binding Sites; D002891:Chromosomes, Human, Pair 21; D002898:Chromosomes, Human, Pair 8; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic; D063990:Gene Ontology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D035683:MicroRNAs / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D060066:Protein Interaction Maps; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D000075142:RUNX1 Translocation Partner 1 Protein; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic; D060449:Wnt Signaling Pathway / Q000235:genetics
D020413:3' Untranslated Regions; D050676:Core Binding Factor Alpha 2 Subunit; D035683:MicroRNAs; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D000075142:RUNX1 Translocation Partner 1 Protein; C493728:RUNX1 protein, human; C082222:RUNX1T1 protein, human; D014157:Transcription Factors
Acute myeloid leukemia; Competing endogenous RNAs; RUNX1T1; Regulatory network; miRNA; t(8;21) AML