Please use this identifier to cite or link to this item:
https://doi.org/10.1186/s13045-017-0507-y
DC Field | Value | |
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dc.title | Inhibition of LIN28B impairs leukemia cell growth and metabolism in acute myeloid leukemia | |
dc.contributor.author | Zhou, J | |
dc.contributor.author | Bi, C | |
dc.contributor.author | Ching, Y.Q | |
dc.contributor.author | Chooi, J.-Y | |
dc.contributor.author | Lu, X | |
dc.contributor.author | Quah, J.Y | |
dc.contributor.author | Toh, S.H.-M | |
dc.contributor.author | Chan, Z.-L | |
dc.contributor.author | Tan, T.Z | |
dc.contributor.author | Chong, P.S | |
dc.contributor.author | Chng, W.-J | |
dc.date.accessioned | 2020-09-01T00:53:26Z | |
dc.date.available | 2020-09-01T00:53:26Z | |
dc.date.issued | 2017 | |
dc.identifier.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 | |
dc.identifier.issn | 17568722 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/173782 | |
dc.description.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). | |
dc.source | Unpaywall 20200831 | |
dc.subject | let 7a | |
dc.subject | LIN28B protein | |
dc.subject | microRNA | |
dc.subject | stem cell factor | |
dc.subject | unclassified drug | |
dc.subject | LIN28B protein, human | |
dc.subject | microRNA | |
dc.subject | mirnlet7 microRNA, human | |
dc.subject | RNA binding protein | |
dc.subject | small interfering RNA | |
dc.subject | acute myeloid leukemia | |
dc.subject | animal experiment | |
dc.subject | animal model | |
dc.subject | animal tissue | |
dc.subject | Article | |
dc.subject | bioinformatics | |
dc.subject | cancer inhibition | |
dc.subject | carcinogenicity | |
dc.subject | cell cycle arrest | |
dc.subject | cell metabolism | |
dc.subject | cell proliferation | |
dc.subject | colony formation | |
dc.subject | controlled study | |
dc.subject | female | |
dc.subject | G2 phase cell cycle checkpoint | |
dc.subject | gene | |
dc.subject | gene function | |
dc.subject | gene overexpression | |
dc.subject | gene silencing | |
dc.subject | gene targeting | |
dc.subject | genetic association | |
dc.subject | hematopoiesis | |
dc.subject | human | |
dc.subject | human cell | |
dc.subject | IGF2BP1 gene | |
dc.subject | in vivo study | |
dc.subject | KDM4A gene | |
dc.subject | leukemia cell | |
dc.subject | leukemogenesis | |
dc.subject | LIN28B gene | |
dc.subject | microarray analysis | |
dc.subject | mouse | |
dc.subject | nonhuman | |
dc.subject | oncogene | |
dc.subject | PSAT1 gene | |
dc.subject | signal transduction | |
dc.subject | tumor xenograft | |
dc.subject | acute myeloid leukemia | |
dc.subject | animal | |
dc.subject | cell cycle checkpoint | |
dc.subject | cell proliferation | |
dc.subject | gene expression regulation | |
dc.subject | genetics | |
dc.subject | metabolism | |
dc.subject | nonobese diabetic mouse | |
dc.subject | pathology | |
dc.subject | RNA interference | |
dc.subject | SCID mouse | |
dc.subject | tumor cell line | |
dc.subject | Animals | |
dc.subject | Cell Cycle Checkpoints | |
dc.subject | Cell Line, Tumor | |
dc.subject | Cell Proliferation | |
dc.subject | Female | |
dc.subject | Gene Expression Regulation, Leukemic | |
dc.subject | Humans | |
dc.subject | Leukemia, Myeloid, Acute | |
dc.subject | Mice | |
dc.subject | Mice, Inbred NOD | |
dc.subject | Mice, SCID | |
dc.subject | MicroRNAs | |
dc.subject | RNA Interference | |
dc.subject | RNA, Small Interfering | |
dc.subject | RNA-Binding Proteins | |
dc.type | Article | |
dc.contributor.department | CANCER SCIENCE INSTITUTE OF SINGAPORE | |
dc.contributor.department | MEDICINE | |
dc.description.doi | 10.1186/s13045-017-0507-y | |
dc.description.sourcetitle | Journal of Hematology and Oncology | |
dc.description.volume | 10 | |
dc.description.issue | 1 | |
dc.description.page | 138 | |
Appears in Collections: | Staff Publications Elements |
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