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

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• 作者：Mindaugas Stoskus^a ; ^b ; ^{mindaugas.stoskus@santa.lt" class="auth_mail" title="E-mail the corresponding author} ; Goda Vaitkeviciene^c ; Audrone Eidukaite^b ; ^c ; Laimonas Griskevicius^a ; ^d
• 关键词：IGF2BP1 ; ETV6/RUNX1 ; t(12 ; 21)(p13 ; q22) ; TEL-AML1
• 刊名：Blood Cells, Molecules and Diseases
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：57
• 期：Complete
• 页码：30-34
• 全文大小：473 K

文摘

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.