PMID- 32066746
OWN - NLM
STAT- MEDLINE
DCOM- 20201116
LR  - 20211204
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 10
IP  - 1
DP  - 2020 Feb 17
TI  - Analysis of TET2 and EZH2 gene functions in chromosome instability in acute 
      myeloid leukemia.
PG  - 2706
LID - 10.1038/s41598-020-59365-w [doi]
LID - 2706
AB  - TET2 and EZH2 play important roles in the epigenetic regulation in many cancers. 
      However, their specific roles in acute myeloid leukemia (AML) pathogenesis remain 
      unknown. Here, the expression, methylation or mutation of EZH2 and TET2 was 
      determined and further correlated with the levels of the chromosome instability 
      (CIN) genes MAD2 and CDC20. We down-regulated EZH2 and TET2 in AML cell lines and 
      assessed the effect on CIN using fluorescence in situ hybridization (FISH). Our 
      results showed that TET2, EZH2, MAD2 and CDC20 were aberrantly expressed in AML 
      patients. The expression level of MAD2 or CDC20 was positively correlated with 
      that of TET2 or EZH2. Hypermethylation of the TET2 gene down-regulated its 
      transcription. Down-regulation of EZH2 or TET2 expression inhibited apoptosis, 
      affected MAD2 and CDC20 expression, and promoted CIN in AML cells. Decitabine 
      treatment restored TET2 methylation and EZH2 transcription and ameliorated CIN in 
      AML. Therefore, TET2 and EZH2 play a tumor-inhibiting role in AML that affects 
      CIN via MAD2 and CDC20.
FAU - Wang, Jingyi
AU  - Wang J
AD  - Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, 
      250012, P.R. China.
AD  - Department of Hematology, Affiliated Hospital of Shandong University of 
      Traditional Chinese Medicine, Jinan, 250011, P.R. China.
FAU - He, Na
AU  - He N
AD  - Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, 
      250012, P.R. China.
FAU - Wang, Ruiqing
AU  - Wang R
AD  - Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, 
      250012, P.R. China.
FAU - Tian, Tian
AU  - Tian T
AD  - Department of Pathology and Microbiology, University of Nebraska Medical Center, 
      Omaha, NE, USA.
FAU - Han, Fengjiao
AU  - Han F
AD  - Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, 
      250012, P.R. China.
FAU - Zhong, Chaoqin
AU  - Zhong C
AD  - Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, 
      250012, P.R. China.
FAU - Zhang, Chen
AU  - Zhang C
AD  - Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, 
      250012, P.R. China.
FAU - Hua, Mingqiang
AU  - Hua M
AD  - Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, 
      250012, P.R. China.
FAU - Ji, Chunyan
AU  - Ji C
AD  - Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, 
      250012, P.R. China.
FAU - Ma, Daoxin
AU  - Ma D
AUID- ORCID: 0000-0003-0664-8441
AD  - Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, 
      250012, P.R. China. daoxinma@sdu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200217
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - 0 (Cdc20 Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (MAD2L1 protein, human)
RN  - 0 (Mad2 Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 156288-95-8 (CDC20 protein, human)
RN  - 776B62CQ27 (Decitabine)
RN  - EC 1.13.11.- (Dioxygenases)
RN  - EC 1.13.11.- (TET2 protein, human)
RN  - EC 2.1.1.43 (EZH2 protein, human)
RN  - EC 2.1.1.43 (Enhancer of Zeste Homolog 2 Protein)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antimetabolites, Antineoplastic/therapeutic use
MH  - Cdc20 Proteins/*genetics/metabolism
MH  - Cell Line, Tumor
MH  - *Chromosomal Instability
MH  - Chromosomes, Human
MH  - DNA Methylation
MH  - DNA-Binding Proteins/antagonists & inhibitors/*genetics/metabolism
MH  - Decitabine/therapeutic use
MH  - Dioxygenases
MH  - Enhancer of Zeste Homolog 2 Protein/antagonists & inhibitors/*genetics/metabolism
MH  - Epigenesis, Genetic
MH  - Female
MH  - *Gene Expression Regulation, Leukemic
MH  - Humans
MH  - Leukemia, Myeloid, Acute/drug therapy/*genetics/metabolism/pathology
MH  - Mad2 Proteins/*genetics/metabolism
MH  - Male
MH  - Middle Aged
MH  - Proto-Oncogene Proteins/antagonists & inhibitors/*genetics/metabolism
MH  - RNA, Small Interfering/genetics/metabolism
MH  - Remission Induction
MH  - Transcription, Genetic
PMC - PMC7026035
COIS- The authors declare no competing interests.
EDAT- 2020/02/19 06:00
MHDA- 2020/11/18 06:00
PMCR- 2020/02/17
CRDT- 2020/02/19 06:00
PHST- 2019/06/04 00:00 [received]
PHST- 2020/01/23 00:00 [accepted]
PHST- 2020/02/19 06:00 [entrez]
PHST- 2020/02/19 06:00 [pubmed]
PHST- 2020/11/18 06:00 [medline]
PHST- 2020/02/17 00:00 [pmc-release]
AID - 10.1038/s41598-020-59365-w [pii]
AID - 59365 [pii]
AID - 10.1038/s41598-020-59365-w [doi]
PST - epublish
SO  - Sci Rep. 2020 Feb 17;10(1):2706. doi: 10.1038/s41598-020-59365-w.