ETV6/RUNX1 transcript is a target of RNA-binding protein IGF2BP1 in t(12;21)(p13;q22)-positive acute lymphoblastic leukemia

Mindaugas Stoskus; Goda Vaitkeviciene; Audrone Eidukaite; Laimonas Griskevicius

doi:10.1016/j.bcmd.2015.11.006

ETV6/RUNX1 transcript is a target of RNA-binding protein IGF2BP1 in t(12;21)(p13;q22)-positive acute lymphoblastic leukemia

Blood Cells Mol Dis. 2016 Mar:57:30-4. doi: 10.1016/j.bcmd.2015.11.006. Epub 2015 Nov 15.

Authors

Mindaugas Stoskus¹, Goda Vaitkeviciene², Audrone Eidukaite³, Laimonas Griskevicius⁴

Affiliations

¹ Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santariskiu Klinikos, Vilnius, Lithuania; Department of Immunology, State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania. Electronic address: mindaugas.stoskus@santa.lt.
² Children's Hospital, Affiliate of Vilnius University Hospital Santariskiu Klinikos, Vilnius, Lithuania.
³ Department of Immunology, State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania; Children's Hospital, Affiliate of Vilnius University Hospital Santariskiu Klinikos, Vilnius, Lithuania.
⁴ Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santariskiu Klinikos, Vilnius, Lithuania; Clinics of Internal, Family Medicine and Oncology, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.

PMID: 26852652
DOI: 10.1016/j.bcmd.2015.11.006

Abstract

The oncofetal RNA-binding protein IGF2BP1 (IGF2 mRNA binding protein 1) is overexpressed in a subset of cancers and promotes cell cycle, migration and aggressive phenotype by regulating post-transcriptionally a number of key mRNAs (e. g, ACTB, CD44, CTNNB1, KRAS, MAPK4, MYC, PTEN and others). IGF2BP1 is also overexpressed in t(12;21)(p13;q22)-positive acute lymphoblastic leukemia (ALL), but the biological significance of this phenomenon has not been addressed so far. We have identified leukemia fusion gene ETV6/RUNX1 mRNA to be highly enriched in immunoprecipitated fraction of endogenous IGF2BP1 from a model cell line REH and t(12;21)(p13;q22)-positive ALL samples. Furthermore, downregulation of IGF2BP1 by two-fold has resulted in a corresponding decrease of ETV6/RUNX1 mRNA validating this transcript as a target of IGF2BP1 protein in t(12;21)(p13;q22)-positive ALL. These data infer that IGF2BP1 is a potent regulator of ETV6/RUNX1 mRNA stability and potentially link this evolutionary-highly conserved protein to cell transformation events in ETV6/RUNX1-mediated leukemogenesis of t(12;21)(p13;q22)-positive ALL.

Keywords: ETV6/RUNX1; IGF2BP1; TEL-AML1; t(12;21)(p13;q22).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinogenesis / genetics
Carcinogenesis / metabolism
Carcinogenesis / pathology
Cell Line, Tumor
Chromosomes, Human, Pair 12
Chromosomes, Human, Pair 21
Core Binding Factor Alpha 2 Subunit / genetics*
Core Binding Factor Alpha 2 Subunit / metabolism
ETS Translocation Variant 6 Protein
Gene Expression Regulation, Leukemic*
Humans
Oncogene Proteins, Fusion / genetics
Oncogene Proteins, Fusion / metabolism
Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism
Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
Protein Binding
Proto-Oncogene Proteins c-ets / genetics*
Proto-Oncogene Proteins c-ets / metabolism
RNA Stability
RNA, Messenger / genetics*
RNA, Messenger / metabolism
RNA-Binding Proteins / genetics*
RNA-Binding Proteins / metabolism
Repressor Proteins / genetics*
Repressor Proteins / metabolism
Translocation, Genetic*

Substances

Core Binding Factor Alpha 2 Subunit
IGF2BP1 protein, human
Oncogene Proteins, Fusion
Proto-Oncogene Proteins c-ets
RNA, Messenger
RNA-Binding Proteins
RUNX1 protein, human
Repressor Proteins