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Genome-wide analyses identify KLF4 as an important negative regulator in T-cell acute lymphoblastic leukemia through directly inhibiting T-cell associated genes

Overview of attention for article published in Molecular Cancer, February 2015
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Title
Genome-wide analyses identify KLF4 as an important negative regulator in T-cell acute lymphoblastic leukemia through directly inhibiting T-cell associated genes
Published in
Molecular Cancer, February 2015
DOI 10.1186/s12943-014-0285-x
Pubmed ID
Authors

Wei Li, Zhiwu Jiang, Tianzhong Li, Xinru Wei, Yi Zheng, Donghai Wu, Lijian Yang, Shaohua Chen, Bing Xu, Mei Zhong, Jue Jiang, Yufeng Hu, Hexiu Su, Minjie Zhang, Xiaojun Huang, Suxia Geng, Jianyu Weng, Xin Du, Pentao Liu, Yangqiu Li, Hudan Liu, Yao Yao, Peng Li

Abstract

BackgroundKruppel-like factor 4 (KLF4) induces tumorigenesis or suppresses tumor growth in a tissue-dependent manner. However, the roles of KLF4 in hematological malignancies and the mechanisms of action are not fully understood.MethodsInducible KLF4-overexpression Jurkat cell line combined with mouse models bearing cell-derived xenografts and primary T-cell acute lymphoblastic leukemia (T-ALL) cells from four patients were used to assess the functional role of KLF4 in T-ALL cells in vitro and in vivo. A genome-wide RNA-seq analysis was conducted to identify genes regulated by KLF4 in T-ALL cells. Chromatin immunoprecipitation (ChIP) PCR was used to determine direct binding sites of KLF4 in T-ALL cells.ResultsHere we reveal that KLF4 induced apoptosis through the BCL2/BCLXL pathway in human T-ALL cell lines and primary T-ALL specimens. In consistence, mice engrafted with KLF4-overexpressing T-ALL cells exhibited prolonged survival. Interestingly, the KLF4-induced apoptosis in T-ALL cells was compromised in xenografts but the invasion capacity of KLF4-expressing T-ALL cells to hosts was dramatically dampened. We found that KLF4 overexpression inhibited T cell-associated genes including NOTCH1, BCL11B, GATA3, and TCF7. Further mechanistic studies revealed that KLF4 directly bound to the promoters of NOTCH1, BCL2, and CXCR4 and suppressed their expression. Additionally, KLF4 induced SUMOylation and degradation of BCL11B.ConclusionsThese results suggest that KLF4 as a major transcription factor that suppresses the expression of T-cell associated genes, thus inhibiting T-ALL progression.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 41 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Japan 1 2%
Italy 1 2%
Unknown 39 95%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 15 37%
Researcher 7 17%
Student > Doctoral Student 4 10%
Student > Bachelor 3 7%
Student > Master 3 7%
Other 4 10%
Unknown 5 12%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 15 37%
Agricultural and Biological Sciences 9 22%
Medicine and Dentistry 5 12%
Chemistry 2 5%
Immunology and Microbiology 2 5%
Other 3 7%
Unknown 5 12%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 04 February 2015.
All research outputs
#22,756,649
of 25,371,288 outputs
Outputs from Molecular Cancer
#1,678
of 1,918 outputs
Outputs of similar age
#308,762
of 360,614 outputs
Outputs of similar age from Molecular Cancer
#40
of 51 outputs
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