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Epigenetic silencing of tumor suppressor miR-3151 contributes to Chinese chronic lymphocytic leukemia by constitutive activation of MADD/ERK and PIK3R2/AKT signaling pathways

Overview of attention for article published in Oncotarget, October 2015
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Title
Epigenetic silencing of tumor suppressor miR-3151 contributes to Chinese chronic lymphocytic leukemia by constitutive activation of MADD/ERK and PIK3R2/AKT signaling pathways
Published in
Oncotarget, October 2015
DOI 10.18632/oncotarget.6251
Pubmed ID
Authors

Lu Qian Wang, Kwan Yeung Wong, Anders Rosèn, Chor Sang Chim

Abstract

We hypothesize that miR-3151, localized to a GWAS-identified chronic lymphocytic leukemia (CLL) risk locus (8q22.3), is a tumor suppressor miRNA silenced by promoter DNA methylation in CLL. The promoter of miR-3151 was methylated in 5/7 (71%) CLL cell lines, 30/98 (31%) diagnostic primary samples, but not normal controls. Methylation of miR-3151 correlated inversely with expression. Treatment with 5-Aza-2'-deoxycytidine led to promoter demethylation and miR-3151 re-expression. Luciferase assay confirmed MAP-kinase activating death domain (MADD) and phosphoinositide-3-kinase, regulatory subunit 2 (PIK3R2) as direct targets of miR-3151. Moreover, restoration of miR-3151 resulted in inhibition of cellular proliferation and enhanced apoptosis, repression of MADD and PIK3R2, downregulation of MEK/ERK and PI3K/AKT signaling, and repression of MCL1. Lastly, miR-3151 methylation was significantly associated with methylation of miR-203 and miR-34b/c in primary CLL samples. Therefore, this study showed that miR-3151 is a tumor suppressive miRNA frequently hypermethylated and hence silenced in CLL. miR-3151 silencing by DNA methylation protected CLL cells from apoptosis through over-expression of its direct targets MADD and PIK3R2, hence constitutive activation of MEK/ERK and PI3K/AKT signaling respectively, and consequently over-expression of MCL1.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 16 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 16 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 5 31%
Student > Bachelor 3 19%
Professor > Associate Professor 2 13%
Unspecified 1 6%
Researcher 1 6%
Other 1 6%
Unknown 3 19%
Readers by discipline Count As %
Agricultural and Biological Sciences 5 31%
Biochemistry, Genetics and Molecular Biology 3 19%
Medicine and Dentistry 3 19%
Chemistry 1 6%
Unspecified 1 6%
Other 0 0%
Unknown 3 19%
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 31 October 2015.
All research outputs
#20,295,099
of 22,831,537 outputs
Outputs from Oncotarget
#10,571
of 14,322 outputs
Outputs of similar age
#238,656
of 284,522 outputs
Outputs of similar age from Oncotarget
#601
of 808 outputs
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