PMID- 36370852
OWN - NLM
STAT- MEDLINE
DCOM- 20221220
LR  - 20221228
IS  - 1090-2422 (Electronic)
IS  - 0014-4827 (Linking)
VI  - 422
IP  - 1
DP  - 2023 Jan 1
TI  - Polycomb group protein BMI1 protects neuroblastoma cells against DNA 
      damage-induced apoptotic cell death.
PG  - 113412
LID - S0014-4827(22)00405-0 [pii]
LID - 10.1016/j.yexcr.2022.113412 [doi]
AB  - The overexpression of BMI1, a polycomb protein, correlates with cancer 
      development and aggressiveness. We previously reported that MYCN-induced BMI1 
      positively regulated neuroblastoma (NB) cell proliferation via the 
      transcriptional inhibition of tumor suppressors in NB cells. To assess the 
      potential of BMI1 as a new target for NB therapy, we examined the effects of 
      reductions in BMI1 on NB cells. BMI1 knockdown (KD) in NB cells significantly 
      induced their differentiation for up to 7 days. BMI1 depletion significantly 
      induced apoptotic NB cell death for up to 14 days along with the activation of 
      p53, increases in p73, and induction of p53 family downstream molecules and 
      pathways, even in p53 mutant cells. BMI1 depletion in vivo markedly suppressed NB 
      xenograft tumor growth. BMI1 reductions activated ATM and increased gamma-H2AX in NB 
      cells. These DNA damage signals and apoptotic cell death were not canceled by the 
      transduction of the polycomb group molecules EZH2 and RING1B. Furthermore, EZH2 
      and RING1B KD did not induce apoptotic NB cell death to the same extent as BMI1 
      KD. Collectively, these results suggest the potential of BMI1 as a target of 
      molecular therapy for NB and confirmed, for the first time, the shared role of 
      PcG proteins in the DNA damage response of NB cells.
CI  - Copyright (c) 2022 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Akita, Nobuhiro
AU  - Akita N
AD  - Department of Hematology and Oncology, Children's Medical Center, Japanese Red 
      Cross Aichi Medical Center Nagoya First Hospital, Japan; Division of Biochemistry 
      and Molecular Carcinogenesis, Chiba Cancer Center Research Institute, Japan; 
      Department of Pediatrics, Chiba University School of Medicine, Japan; Research 
      Institute for Clinical Oncology, Saitama Cancer Center, Japan.
FAU - Okada, Ryu
AU  - Okada R
AD  - Research Institute for Clinical Oncology, Saitama Cancer Center, Japan; 
      Department of Graduate School of Science and Engineering, Saitama University, 
      Japan.
FAU - Mukae, Kyosuke
AU  - Mukae K
AD  - Research Institute for Clinical Oncology, Saitama Cancer Center, Japan.
FAU - Sugino, Ryuichi P
AU  - Sugino RP
AD  - Research Institute for Clinical Oncology, Saitama Cancer Center, Japan.
FAU - Takenobu, Hisanori
AU  - Takenobu H
AD  - Division of Biochemistry and Molecular Carcinogenesis, Chiba Cancer Center 
      Research Institute, Japan; Research Institute for Clinical Oncology, Saitama 
      Cancer Center, Japan. Electronic address: takenobu@saitama-pho.jp.
FAU - Chikaraishi, Koji
AU  - Chikaraishi K
AD  - Department of Pediatrics, Chiba University School of Medicine, Japan; Research 
      Institute for Clinical Oncology, Saitama Cancer Center, Japan.
FAU - Ochiai, Hidemasa
AU  - Ochiai H
AD  - Department of Pediatrics, Chiba University School of Medicine, Japan.
FAU - Yamaguchi, Yohko
AU  - Yamaguchi Y
AD  - Division of Biochemistry and Molecular Carcinogenesis, Chiba Cancer Center 
      Research Institute, Japan; Department of Molecular Toxicology, Faculty of 
      Pharmaceutical Sciences, Toho University, Japan.
FAU - Ohira, Miki
AU  - Ohira M
AD  - Division of Biochemistry and Molecular Carcinogenesis, Chiba Cancer Center 
      Research Institute, Japan; Research Institute for Clinical Oncology, Saitama 
      Cancer Center, Japan.
FAU - Koseki, Haruhiko
AU  - Koseki H
AD  - Developmental Genetics Group, RIKEN Research Center for Allergy and Immunology, 
      Japan.
FAU - Kamijo, Takehiko
AU  - Kamijo T
AD  - Division of Biochemistry and Molecular Carcinogenesis, Chiba Cancer Center 
      Research Institute, Japan; Research Institute for Clinical Oncology, Saitama 
      Cancer Center, Japan; Department of Graduate School of Science and Engineering, 
      Saitama University, Japan. Electronic address: tkamijo@saitama-pho.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221109
PL  - United States
TA  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (Polycomb-Group Proteins)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (BMI1 protein, human)
RN  - EC 2.3.2.27 (Polycomb Repressive Complex 1)
SB  - IM
MH  - Humans
MH  - Polycomb-Group Proteins/genetics
MH  - *Tumor Suppressor Protein p53/genetics/metabolism
MH  - Cell Line, Tumor
MH  - *Neuroblastoma/pathology
MH  - Apoptosis/genetics
MH  - DNA Damage/genetics
MH  - Polycomb Repressive Complex 1/genetics/metabolism
OTO - NOTNLM
OT  - Apoptosis
OT  - BMI1
OT  - DNA damage
OT  - Neuroblastoma
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2022/11/13 06:00
MHDA- 2022/12/21 06:00
CRDT- 2022/11/12 19:33
PHST- 2022/05/12 00:00 [received]
PHST- 2022/10/31 00:00 [revised]
PHST- 2022/11/05 00:00 [accepted]
PHST- 2022/11/13 06:00 [pubmed]
PHST- 2022/12/21 06:00 [medline]
PHST- 2022/11/12 19:33 [entrez]
AID - S0014-4827(22)00405-0 [pii]
AID - 10.1016/j.yexcr.2022.113412 [doi]
PST - ppublish
SO  - Exp Cell Res. 2023 Jan 1;422(1):113412. doi: 10.1016/j.yexcr.2022.113412. Epub 
      2022 Nov 9.