PMID- 38296629
OWN - NLM
STAT- MEDLINE
DCOM- 20240320
LR  - 20240401
IS  - 1469-9001 (Electronic)
IS  - 1355-8382 (Print)
IS  - 1355-8382 (Linking)
VI  - 30
IP  - 4
DP  - 2024 Mar 18
TI  - Histone lysine demethylase KDM5B facilitates proliferation and suppresses 
      apoptosis in human acute myeloid leukemia cells through the miR-140-3p/BCL2 axis.
PG  - 435-447
LID - 10.1261/rna.079865.123 [doi]
AB  - The histone lysine demethylase KDM5B is frequently up-regulated in various human 
      cancer cells. However, its expression and functional role in human acute myeloid 
      leukemia (AML) cells remain unclear. Here, we found that the expression level of 
      KDM5B is high in primary human AML cells. We have demonstrated that knocking down 
      KDM5B leads to apoptosis and impairs proliferation in primary human AML and some 
      human AML cell lines. We further identified miR-140-3p as a downstream target 
      gene of KDM5B. KDM5B expression was inversely correlated with the miR-140-3p 
      level in primary human AML cells. Molecular studies showed that silencing KDM5B 
      enhanced H3K4 trimethylation (H3K4me3) at the promoter of miR-140-3p, leading to 
      high expression of miR-140-3p, which in turn inhibited B-cell CLL/lymphoma 2 
      (BCL2) expression. Finally, we demonstrate that the defective proliferation 
      induced by KDM5B knockdown (KD) can be rescued with the miR-140-3p inhibitor or 
      enhanced by combining KDM5B KD with a BCL2 inhibitor. Altogether, our data 
      support the conclusion that KDM5B promotes tumorigenesis in human AML cells 
      through the miR-140-3p/BCL2 axis. Targeting the KDM5B/miR-140-3p/BCL2 pathway may 
      hold therapeutic promise for treating human AML.
CI  - (c) 2024 Huang et al.; Published by Cold Spring Harbor Laboratory Press for the RNA 
      Society.
FAU - Huang, Jiaojuan
AU  - Huang J
AUID- ORCID: 0009-0005-2154-0481
AD  - School of Basic Medicine, Tongji Medical College, Huazhong University of Science 
      and Technology, Wuhan 430030, China.
FAU - Jin, Shuiling
AU  - Jin S
AUID- ORCID: 0000-0001-7330-7140
AD  - Department of Oncology, The First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou 450052, China.
FAU - Guo, Rongqun
AU  - Guo R
AUID- ORCID: 0000-0002-1238-4772
AD  - Department of Hematology, The First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou 450052, China.
FAU - Wu, Wei
AU  - Wu W
AUID- ORCID: 0000-0002-4821-5946
AD  - Department of Clinical Laboratory, Institute of Translational Medicine, Renmin 
      Hospital of Wuhan University, Wuhan 430060, China.
FAU - Yang, Chengxuan
AU  - Yang C
AD  - Department of Galactophore, Xinxiang First People's Hospital, Xinxiang 453000, 
      China.
FAU - Qin, Yali
AU  - Qin Y
AUID- ORCID: 0009-0002-0220-1482
AD  - School of Basic Medicine, Tongji Medical College, Huazhong University of Science 
      and Technology, Wuhan 430030, China.
FAU - Chen, Qingchuan
AU  - Chen Q
AUID- ORCID: 0009-0007-4846-1091
AD  - School of Basic Medicine, Tongji Medical College, Huazhong University of Science 
      and Technology, Wuhan 430030, China.
FAU - He, Ximiao
AU  - He X
AUID- ORCID: 0000-0003-1253-5275
AD  - School of Basic Medicine, Tongji Medical College, Huazhong University of Science 
      and Technology, Wuhan 430030, China.
FAU - Qu, Jing
AU  - Qu J
AUID- ORCID: 0000-0003-0468-5038
AD  - School of Basic Medicine, Tongji Medical College, Huazhong University of Science 
      and Technology, Wuhan 430030, China jingqu@hust.edu.cn zhenhua@hust.edu.cn.
FAU - Yang, Zhenhua
AU  - Yang Z
AUID- ORCID: 0000-0002-8204-0852
AD  - School of Basic Medicine, Tongji Medical College, Huazhong University of Science 
      and Technology, Wuhan 430030, China jingqu@hust.edu.cn zhenhua@hust.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20240318
PL  - United States
TA  - RNA
JT  - RNA (New York, N.Y.)
JID - 9509184
RN  - 0 (BCL2 protein, human)
RN  - EC 1.14.11.- (Histone Demethylases)
RN  - EC 1.14.11.- (Jumonji Domain-Containing Histone Demethylases)
RN  - EC 1.14.11.- (KDM5B protein, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Mirn140 microRNA, human)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Repressor Proteins)
SB  - IM
MH  - Humans
MH  - Apoptosis/genetics
MH  - Cell Line, Tumor
MH  - Cell Proliferation/genetics
MH  - Gene Expression Regulation, Neoplastic
MH  - Histone Demethylases/genetics/metabolism
MH  - Jumonji Domain-Containing Histone Demethylases/genetics/metabolism
MH  - *Leukemia, Myeloid, Acute/genetics
MH  - *MicroRNAs/genetics/metabolism
MH  - Nuclear Proteins/genetics/metabolism
MH  - Proto-Oncogene Proteins c-bcl-2/genetics/metabolism
MH  - Repressor Proteins/genetics
PMC - PMC10946434
OTO - NOTNLM
OT  - BCL2
OT  - KDM5B
OT  - acute myeloid leukemia
OT  - histone H3K4 methylation
OT  - miR-140-3p
EDAT- 2024/02/01 00:42
MHDA- 2024/03/20 06:45
PMCR- 2025/04/01
CRDT- 2024/01/31 21:37
PHST- 2023/10/04 00:00 [received]
PHST- 2024/01/21 00:00 [accepted]
PHST- 2025/04/01 00:00 [pmc-release]
PHST- 2024/03/20 06:45 [medline]
PHST- 2024/02/01 00:42 [pubmed]
PHST- 2024/01/31 21:37 [entrez]
AID - rna.079865.123 [pii]
AID - RA [pii]
AID - 10.1261/rna.079865.123 [doi]
PST - epublish
SO  - RNA. 2024 Mar 18;30(4):435-447. doi: 10.1261/rna.079865.123.