PMID- 31358016
OWN - NLM
STAT- MEDLINE
DCOM- 20200615
LR  - 20200615
IS  - 1478-811X (Electronic)
IS  - 1478-811X (Linking)
VI  - 17
IP  - 1
DP  - 2019 Jul 29
TI  - Histone deacetylase 1 induced by neddylation inhibition contributes to drug 
      resistance in acute myelogenous leukemia.
PG  - 86
LID - 10.1186/s12964-019-0393-8 [doi]
LID - 86
AB  - OBJECTIVE: This study aimed to investigate the function and mechanism of 
      neddylation of HDAC1 underlying drug resistance of AML cells. METHODS: Evaluation 
      experiments of effects of HDAC1 on drug resistance of AML cells were performed 
      with AML cell transfected with constructs overexpressing HDAC1 or multi-drug 
      resistance AML cells transfected with siRNA for HDAC1 through observing cell 
      viability, percentage of apoptotic cell, doxorubicin-releasing index and 
      multidrug resistance associated protein 1 (MRP1) expression. Neddylation or 
      ubiquitination of HDAC1 was determined by immunoprecipitation or Ni2(+) pull down 
      assay followed by western blot. The role of HDAC1 was in vivo confirmed by 
      xenograft in mice. RESULTS: HDAC1 was significantly upregulated in refractory AML 
      patients, and in drug-resistant AML cells (HL-60/ADM and K562/A02). Intracellular 
      HDAC1 expression promoted doxorubicin resistance of HL-60, K562, and primary bone 
      marrow cells (BMCs) of remission AML patients as shown by increasing cell 
      viability and doxorubicin-releasing index, inhibiting cell apoptosis. Moreover, 
      HDAC1 protein level in AML cells was regulated by the Nedd8-mediated neddylation 
      and ubiquitination, which further promoted HDAC1 degradation. In vivo, HDAC1 
      overexpression significantly increased doxorubicin resistance; while HDACs 
      inhibitor Panobinostat markedly improved the inhibitory effect of doxorubicin on 
      tumor growth. Furthermore, HDAC1 silencing by Panobinostat and/or lentivirus 
      mediated RNA interference against HDAC1 effectively reduced doxorubicin 
      resistance, resulting in the inhibition of tumor growth in AML bearing mice. 
      CONCLUSION: Our findings suggested that HDAC1 contributed to the multidrug 
      resistance of AML and its function turnover was regulated, at least in part, by 
      post-translational modifications, including neddylation and ubiquitination.
FAU - Lai, Qiu-Yu
AU  - Lai QY
AD  - Department of Hematology, ZhuJiang Hospital of Southern Medical Univeristy, No. 
      253 GongyeDadaoZhong, 510280, Guangzhou, Guangdong, People's Republic of China.
FAU - He, Ying-Zhi
AU  - He YZ
AD  - Department of Hematology, ZhuJiang Hospital of Southern Medical Univeristy, No. 
      253 GongyeDadaoZhong, 510280, Guangzhou, Guangdong, People's Republic of China.
FAU - Peng, Xiong-Wen
AU  - Peng XW
AD  - Department of Hematologic Oncology, Sun Yat-sen University Cancer Center, 
      Guangzhou, China.
FAU - Zhou, Xuan
AU  - Zhou X
AD  - Department of Hematology, ZhuJiang Hospital of Southern Medical Univeristy, No. 
      253 GongyeDadaoZhong, 510280, Guangzhou, Guangdong, People's Republic of China.
FAU - Liang, Dan
AU  - Liang D
AD  - Department of Hematology, ZhuJiang Hospital of Southern Medical Univeristy, No. 
      253 GongyeDadaoZhong, 510280, Guangzhou, Guangdong, People's Republic of China.
FAU - Wang, Liang
AU  - Wang L
AD  - Department of Hematology, ZhuJiang Hospital of Southern Medical Univeristy, No. 
      253 GongyeDadaoZhong, 510280, Guangzhou, Guangdong, People's Republic of China. 
      wangliangzjyy@126.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190729
PL  - England
TA  - Cell Commun Signal
JT  - Cell communication and signaling : CCS
JID - 101170464
RN  - 0 (NEDD8 Protein)
RN  - 80168379AG (Doxorubicin)
RN  - EC 3.5.1.98 (Histone Deacetylase 1)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Animals
MH  - Cell Line, Tumor
MH  - Doxorubicin/pharmacology
MH  - *Drug Resistance, Neoplasm
MH  - Enzyme Induction/drug effects
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Gene Knockdown Techniques
MH  - Histone Deacetylase 1/*biosynthesis/deficiency/genetics/*metabolism
MH  - Humans
MH  - Intracellular Space/drug effects/metabolism
MH  - Leukemia, Myeloid, Acute/drug therapy/*pathology
MH  - Male
MH  - Mice
MH  - Middle Aged
MH  - NEDD8 Protein/metabolism
MH  - Protein Processing, Post-Translational/*drug effects
MH  - Ubiquitination/drug effects
MH  - Xenograft Model Antitumor Assays
MH  - Young Adult
PMC - PMC6664585
OTO - NOTNLM
OT  - Acute myelogenous leukemia
OT  - Drug resistance
OT  - HDAC1
OT  - Neddylation
OT  - Ubiquitination
COIS- The authors declare that they have no competing interests.
EDAT- 2019/07/31 06:00
MHDA- 2020/06/17 06:00
PMCR- 2019/07/29
CRDT- 2019/07/31 06:00
PHST- 2019/02/25 00:00 [received]
PHST- 2019/07/15 00:00 [accepted]
PHST- 2019/07/31 06:00 [entrez]
PHST- 2019/07/31 06:00 [pubmed]
PHST- 2020/06/17 06:00 [medline]
PHST- 2019/07/29 00:00 [pmc-release]
AID - 10.1186/s12964-019-0393-8 [pii]
AID - 393 [pii]
AID - 10.1186/s12964-019-0393-8 [doi]
PST - epublish
SO  - Cell Commun Signal. 2019 Jul 29;17(1):86. doi: 10.1186/s12964-019-0393-8.