Stoskus Mindaugas, Vaitkeviciene Goda, Eidukaite Audrone, Griskevicius Laimonas
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.
Children's Hospital, Affiliate of Vilnius University Hospital Santariskiu Klinikos, Vilnius, Lithuania.
Blood Cells Mol Dis. 2016 Mar;57:30-4. doi: 10.1016/j.bcmd.2015.11.006. Epub 2015 Nov 15.
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.
癌胚RNA结合蛋白IGF2BP1（胰岛素样生长因子2信使核糖核酸结合蛋白1）在部分癌症中过表达，并通过转录后调控多个关键信使核糖核酸（如肌动蛋白β、CD44、β-连环蛋白、KRAS、丝裂原活化蛋白激酶4、MYC、磷酸酶和张力蛋白同源物等）来促进细胞周期、迁移和侵袭性表型。IGF2BP1在t(12;21)(p13;q22)阳性急性淋巴细胞白血病（ALL）中也过表达，但这一现象的生物学意义迄今尚未得到阐明。我们已确定白血病融合基因ETV6/RUNX1信使核糖核酸在模型细胞系REH和t(12;21)(p13;q22)阳性ALL样本的内源性IGF2BP1免疫沉淀组分中高度富集。此外，IGF2BP1下调两倍导致ETV6/RUNX1信使核糖核酸相应减少，证实该转录本是t(12;21)(p13;q22)阳性ALL中IGF2BP1蛋白的一个靶点。这些数据表明IGF2BP1是ETV6/RUNX1信使核糖核酸稳定性的有效调节因子，并可能将这种进化上高度保守的蛋白与t(12;21)(p13;q22)阳性ALL中ETV6/RUNX1介导的白血病发生过程中的细胞转化事件联系起来。
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