Please use this identifier to cite or link to this item: https://doi.org/10.1186/s13045-017-0507-y
Title: Inhibition of LIN28B impairs leukemia cell growth and metabolism in acute myeloid leukemia
Authors: Zhou, J 
Bi, C
Ching, Y.Q 
Chooi, J.-Y 
Lu, X
Quah, J.Y 
Toh, S.H.-M 
Chan, Z.-L
Tan, T.Z 
Chong, P.S 
Chng, W.-J 
Keywords: let 7a
LIN28B protein
microRNA
stem cell factor
unclassified drug
LIN28B protein, human
microRNA
mirnlet7 microRNA, human
RNA binding protein
small interfering RNA
acute myeloid leukemia
animal experiment
animal model
animal tissue
Article
bioinformatics
cancer inhibition
carcinogenicity
cell cycle arrest
cell metabolism
cell proliferation
colony formation
controlled study
female
G2 phase cell cycle checkpoint
gene
gene function
gene overexpression
gene silencing
gene targeting
genetic association
hematopoiesis
human
human cell
IGF2BP1 gene
in vivo study
KDM4A gene
leukemia cell
leukemogenesis
LIN28B gene
microarray analysis
mouse
nonhuman
oncogene
PSAT1 gene
signal transduction
tumor xenograft
acute myeloid leukemia
animal
cell cycle checkpoint
cell proliferation
gene expression regulation
genetics
metabolism
nonobese diabetic mouse
pathology
RNA interference
SCID mouse
tumor cell line
Animals
Cell Cycle Checkpoints
Cell Line, Tumor
Cell Proliferation
Female
Gene Expression Regulation, Leukemic
Humans
Leukemia, Myeloid, Acute
Mice
Mice, Inbred NOD
Mice, SCID
MicroRNAs
RNA Interference
RNA, Small Interfering
RNA-Binding Proteins
Issue Date: 2017
Citation: Zhou, J, Bi, C, Ching, Y.Q, Chooi, J.-Y, Lu, X, Quah, J.Y, Toh, S.H.-M, Chan, Z.-L, Tan, T.Z, Chong, P.S, Chng, W.-J (2017). Inhibition of LIN28B impairs leukemia cell growth and metabolism in acute myeloid leukemia. Journal of Hematology and Oncology 10 (1) : 138. ScholarBank@NUS Repository. https://doi.org/10.1186/s13045-017-0507-y
Abstract: Background: Current conventional chemotherapy for acute myeloid leukemia (AML) can achieve remission in over 70% of patients, but a majority of them will relapse within 5 years despite continued treatment. The relapse is postulated to be due to leukemia stem cells (LSCs), which are different from normal hematopoietic stem cells (HSCs). LIN28B is microRNA regulator and stem cell reprogramming factor. Overexpression of LIN28B has been associated with advance human malignancies and cancer stem cells (CSCs), including AML. However, the molecular mechanism by which LIN28B contributes to the development of AML remains largely elusive. Methods: We modulated LIN28B expression in AML and non-leukemic cells and investigated functional consequences in cell proliferation, cell cycle, and colony-forming assays. We performed a microarray-based analysis for LIN28B-silencing cells and interrogated gene expression data with different bioinformatic tools. AML mouse xenograft model was used to examine the in vivo function of LIN28B. Results: We demonstrated that targeting LIN28B in AML cells resulted in cell cycle arrest, inhibition of cell proliferation and colony formation, which was induced by de-repression of let-7a miRNA. On the other hand, overexpression of LIN28B promoted cell proliferation. Data point to a mechanism where that inhibition of LIN28B induces metabolic changes in AML cells. IGF2BP1 was confirmed to be a novel downstream target of LIN28B via let-7 miRNA in AML. Notably, ectopic expression of LIN28B increased tumorigenicity, while silencing LIN28B led to slow tumor growth in vivo. Conclusions: In sum, these results uncover a novel mechanism of an important regulatory signaling, LIN28B/let-7/IGF2BP1, in leukemogenesis and provide a rationale to target this pathway as effective therapeutic strategy. © 2017 The Author(s).
Source Title: Journal of Hematology and Oncology
URI: https://scholarbank.nus.edu.sg/handle/10635/173782
ISSN: 17568722
DOI: 10.1186/s13045-017-0507-y
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