TY - JOUR
T1 - WDR5 high expression and its effect on tumorigenesis in leukemia
AU - Ge, Zheng
AU - Song, Evelyn J.
AU - Kawasawa, Yuka Imamura
AU - Li, Jianyong
AU - Dovat, Sinisa
AU - Song, Chunhua
N1 - Funding Information:
We thank Justin Olson for his English grammar correction. This work is supported by The National Natural Science Foundation of China (81270613, 30973376); Jiangsu Province Key Medical Talents (RC2011077); The Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry (39th); China Postdoctoral Science Foundation (20090461134 ); Special grade of the financial support from China Postdoctoral Science Foundation (201003598); The Six Great Talent Peak Plan of Jiangsu (2010-WS-024); The Scientific Research Foundation for the Returned Overseas Chinese Scholars, Nanjing Municipal Bureau of Personnel (2009); Southeast University Basic Research fund (2242016 K40143) (to Z.G.); also supported partially by the Four Diamonds Fund of the Pennsylvania State University, College of Medicine, and the John Wawrynovic Leukemia Research Scholar Endowment (to S.D. and C.S.)
PY - 2016
Y1 - 2016
N2 - WD repeat domain 5 (WDR5) plays an important role in various biological functions through the epigenetic regulation of gene transcription. However, the oncogenic effect of WDR5 in leukemia remains largely unknown. Here, we found WDR5 expression is increased in leukemia patients. High expression of WDR5 is associated with high risk leukemia; Patients with WDR5 and MLL1 high expression have poor complete remission rate. We further identified the global genomic binding of WDR5 in leukemic cells and found the genomic co-localization of WDR5 binding with H3K4me3 enrichment. Moreover, WDR5 knockdown by shRNA suppresses cell proliferation, induces apoptosis, inhibits the expression of WDR5 targets, and blocks the H3K4me3 enrichment on the promoter of its targets. We also observed the positive correlation of WDR5 expression with these targets in the cohort study of leukemia patients. Our data reveal that WDR5 may have oncogenic effect and WDR5-mediated H3K4 methylation plays an important role in leukemogenesis.
AB - WD repeat domain 5 (WDR5) plays an important role in various biological functions through the epigenetic regulation of gene transcription. However, the oncogenic effect of WDR5 in leukemia remains largely unknown. Here, we found WDR5 expression is increased in leukemia patients. High expression of WDR5 is associated with high risk leukemia; Patients with WDR5 and MLL1 high expression have poor complete remission rate. We further identified the global genomic binding of WDR5 in leukemic cells and found the genomic co-localization of WDR5 binding with H3K4me3 enrichment. Moreover, WDR5 knockdown by shRNA suppresses cell proliferation, induces apoptosis, inhibits the expression of WDR5 targets, and blocks the H3K4me3 enrichment on the promoter of its targets. We also observed the positive correlation of WDR5 expression with these targets in the cohort study of leukemia patients. Our data reveal that WDR5 may have oncogenic effect and WDR5-mediated H3K4 methylation plays an important role in leukemogenesis.
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U2 - 10.18632/oncotarget.9312
DO - 10.18632/oncotarget.9312
M3 - Article
C2 - 27192115
AN - SCOPUS:84978140781
SN - 1949-2553
VL - 7
SP - 37740
EP - 37754
JO - Oncotarget
JF - Oncotarget
IS - 25
ER -