IGF2BP2 promotes lncRNA DANCR stability mediated glycolysis and affects the progression of FLT3-ITD + acute myeloid leukemia

• Published in: Apoptosis (London) Vol. 28; no. 7-8; pp. 1035 - 1047
• Main Authors: Wu, Shenghao, Chi, Changwei, Weng, Shanshan, Zhou, Wenjin, Liu, Zhen
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2023; Springer; Springer Nature B.V
• Subjects: Acute myeloid leukemia; Apoptosis; Apoptosis - genetics; Biochemistry; Biomarkers; Biomarkers - metabolism; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cancer therapies; Cell Biology; Cell proliferation; Design; Drug development; fms-Like Tyrosine Kinase 3 - genetics; fms-Like Tyrosine Kinase 3 - metabolism; fms-Like Tyrosine Kinase 3 - therapeutic use; Glucose metabolism; Glycolysis; Glycolysis - genetics; Humans; Kinases; Leukemia; Leukemia, Myeloid, Acute - drug therapy; Medical prognosis; Methyltransferases; MicroRNAs; Mutation; Oncology; Proteins; RNA; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Stability; Tumors; Vectors (Biology); Virology; Glycolysis; N6-methyladenosine; IGF2BP2; FLT3-ITD; Acute myeloid leukemia (AML)
• ISSN: 1360-8185; 1573-675X
• DOI: 10.1007/s10495-023-01846-0

Internal tandem duplication (ITD) is the most common type of FLT3 mutation (FLT3-ITD), accounting for about 25% of AML patients. The expression of DANCR in FLT3-ITD AML had not been paid attention to, and whether its regulatory relationship with IGF2BP2 can affect the progression of FLT3-ITD AML was unclear. Our study sought to verify the biological role of IGF2BP2 as an m6A reading protein in FLT3-ITD AML. To further explore the role and mechanism of DANCR in AML, and provide a basis for the screening of biomarkers and the development of targeted drugs. The results show that IGF2BP2 was upregulated in FLT3-ITD+ AML patients and cells. Si-IGF2BP2 could inhibit the proliferation, glycolytic and promote the apoptosis in MV4-11 cells. IGF2BP2 could promote the DANCR RNA stability. This discovery will provide new horizons for early screening and targeted therapy of FLT3-ITD+ AML.