Assessing the miRNA sponge potential of RUNX1T1 in t(8;21) acute myeloid leukemia

Alexander Junge; Roza Zandi; Jakob Hull Havgaard; Jan Gorodkin; Jack Bernard Cowland

doi:10.1016/j.gene.2017.03.015

Assessing the miRNA sponge potential of RUNX1T1 in t(8;21) acute myeloid leukemia

Alexander Junge, Roza Zandi, Jakob Hull Havgaard, Jan Gorodkin^*, Jack Bernard Cowland

^*Corresponding author for this work

8 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Gene
Volume	615
Pages (from-to)	35-40
Number of pages	6
ISSN	0378-1119
DOIs	https://doi.org/10.1016/j.gene.2017.03.015
Publication status	Published - 2017

Keywords

Acute myeloid leukemia
Competing endogenous RNAs
miRNA
Regulatory network
RUNX1T1
t(8;21) AML

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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@article{61c8608de87f4fc8b457375cdbeb2bed,

title = "Assessing the miRNA sponge potential of RUNX1T1 in t(8;21) acute myeloid leukemia",

abstract = "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.",

keywords = "Acute myeloid leukemia, Competing endogenous RNAs, miRNA, Regulatory network, RUNX1T1, t(8;21) AML",

author = "Alexander Junge and Roza Zandi and Havgaard, {Jakob Hull} and Jan Gorodkin and Cowland, {Jack Bernard}",

year = "2017",

doi = "10.1016/j.gene.2017.03.015",

language = "English",

volume = "615",

pages = "35--40",

journal = "Gene",

issn = "0378-1119",

publisher = "Elsevier",

}

TY - JOUR

T1 - Assessing the miRNA sponge potential of RUNX1T1 in t(8;21) acute myeloid leukemia

AU - Junge, Alexander

AU - Zandi, Roza

AU - Havgaard, Jakob Hull

AU - Gorodkin, Jan

AU - Cowland, Jack Bernard

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Acute myeloid leukemia

KW - Competing endogenous RNAs

KW - miRNA

KW - Regulatory network

KW - RUNX1T1

KW - t(8;21) AML

U2 - 10.1016/j.gene.2017.03.015

DO - 10.1016/j.gene.2017.03.015

M3 - Journal article

C2 - 28322996

AN - SCOPUS:85016394389

SN - 0378-1119

VL - 615

SP - 35

EP - 40

JO - Gene

JF - Gene

ER -

Assessing the miRNA sponge potential of RUNX1T1 in t(8;21) acute myeloid leukemia

Abstract

Keywords

UN SDGs

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