PMID- 38465861
OWN - NLM
STAT- MEDLINE
DCOM- 20240312
LR  - 20240315
IS  - 1555-8576 (Electronic)
IS  - 1538-4047 (Print)
IS  - 1538-4047 (Linking)
VI  - 25
IP  - 1
DP  - 2024 Dec 31
TI  - Repression of the SUMO-conjugating enzyme UBC9 is associated with lowered double 
      minutes and reduced tumor progression.
PG  - 2323768
LID - 10.1080/15384047.2024.2323768 [doi]
LID - 2323768
AB  - Double minutes (DMs), extrachromosomal gene fragments found within certain 
      tumors, have been noted to carry onco- and drug resistance genes contributing to 
      tumor pathogenesis and progression. After screening for SUMO-related molecule 
      expression within various tumor sample and cell line databases, we found that 
      SUMO-conjugating enzyme UBC9 has been associated with genome instability and 
      tumor cell DM counts, which was confirmed both in vitro and in vivo. Karyotyping 
      determined DM counts post-UBC9 knockdown or SUMOylation inhibitor 2-D08, while 
      RT-qPCR and Western blot were used to measure DM-carried gene expression in 
      vitro. In vivo, fluorescence in situ hybridization (FISH) identified micronucleus 
      (MN) expulsion. Western blot and immunofluorescence staining were then used to 
      determine DNA damage extent, and a reporter plasmid system was constructed to 
      detect changes in homologous recombination (HR) and non-homologous end joining 
      (NHEJ) pathways. Our research has shown that UBC9 inhibition is able to attenuate 
      DM formation and lower DM-carried gene expression, in turn reducing tumor growth 
      and malignant phenotype, via MN efflux of DMs and lowering NHEJ activity to 
      increase DNA damage. These findings thus reveal a relationship between heightened 
      UBC9 activity, increased DM counts, and tumor progression, providing a potential 
      approach for targeted therapies, via UBC9 inhibition.
FAU - Wang, Yusi
AU  - Wang Y
AD  - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.
AD  - Key Laboratory of Preservation of Human Genetic Resources and Disease Control in 
      China, Harbin Medical University, Harbin, China.
FAU - Zou, Hongyan
AU  - Zou H
AD  - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.
AD  - Key Laboratory of Preservation of Human Genetic Resources and Disease Control in 
      China, Harbin Medical University, Harbin, China.
FAU - Ji, Wei
AU  - Ji W
AD  - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.
AD  - Key Laboratory of Preservation of Human Genetic Resources and Disease Control in 
      China, Harbin Medical University, Harbin, China.
FAU - Huang, Min
AU  - Huang M
AD  - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.
AD  - Key Laboratory of Preservation of Human Genetic Resources and Disease Control in 
      China, Harbin Medical University, Harbin, China.
FAU - You, Benhui
AU  - You B
AD  - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.
AD  - Key Laboratory of Preservation of Human Genetic Resources and Disease Control in 
      China, Harbin Medical University, Harbin, China.
FAU - Sun, Nan
AU  - Sun N
AD  - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.
AD  - Key Laboratory of Preservation of Human Genetic Resources and Disease Control in 
      China, Harbin Medical University, Harbin, China.
FAU - Qiao, Yuandong
AU  - Qiao Y
AD  - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.
AD  - Key Laboratory of Preservation of Human Genetic Resources and Disease Control in 
      China, Harbin Medical University, Harbin, China.
FAU - Liu, Peng
AU  - Liu P
AD  - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.
AD  - Key Laboratory of Preservation of Human Genetic Resources and Disease Control in 
      China, Harbin Medical University, Harbin, China.
FAU - Xu, Lidan
AU  - Xu L
AD  - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.
AD  - Key Laboratory of Preservation of Human Genetic Resources and Disease Control in 
      China, Harbin Medical University, Harbin, China.
FAU - Zhang, Xuelong
AU  - Zhang X
AD  - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.
AD  - Key Laboratory of Preservation of Human Genetic Resources and Disease Control in 
      China, Harbin Medical University, Harbin, China.
FAU - Cai, Mengdi
AU  - Cai M
AD  - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.
AD  - Key Laboratory of Preservation of Human Genetic Resources and Disease Control in 
      China, Harbin Medical University, Harbin, China.
FAU - Kuang, Ye
AU  - Kuang Y
AD  - Department of Gynecology and Obstetrics, The 2nd Affiliated Hospital of Harbin 
      Medical University, Harbin, China.
FAU - Fu, Songbin
AU  - Fu S
AD  - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.
AD  - Key Laboratory of Preservation of Human Genetic Resources and Disease Control in 
      China, Harbin Medical University, Harbin, China.
FAU - Sun, Wenjing
AU  - Sun W
AD  - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.
AD  - Key Laboratory of Preservation of Human Genetic Resources and Disease Control in 
      China, Harbin Medical University, Harbin, China.
FAU - Jia, Xueyuan
AU  - Jia X
AD  - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.
AD  - Key Laboratory of Preservation of Human Genetic Resources and Disease Control in 
      China, Harbin Medical University, Harbin, China.
FAU - Wu, Jie
AU  - Wu J
AUID- ORCID: 0000-0003-1525-7864
AD  - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.
AD  - Key Laboratory of Preservation of Human Genetic Resources and Disease Control in 
      China, Harbin Medical University, Harbin, China.
AD  - Future Medical Laboratory, The 2nd Affiliated Hospital of Harbin Medical 
      University, Harbin, China.
LA  - eng
PT  - Journal Article
DEP - 20240311
PL  - United States
TA  - Cancer Biol Ther
JT  - Cancer biology & therapy
JID - 101137842
RN  - EC 6.3.2.- (ubiquitin-conjugating enzyme UBC9)
SB  - IM
MH  - Humans
MH  - Cell Nucleus
MH  - *Chromosome Aberrations
MH  - *DNA Damage
MH  - In Situ Hybridization, Fluorescence
PMC - PMC10936631
OTO - NOTNLM
OT  - DNA damage repair
OT  - SUMOylation
OT  - UBC9
OT  - double minutes
OT  - genome instability
COIS- No potential conflict of interest was reported by the author(s).
EDAT- 2024/03/11 12:43
MHDA- 2024/03/12 06:43
PMCR- 2024/03/11
CRDT- 2024/03/11 08:23
PHST- 2024/03/12 06:43 [medline]
PHST- 2024/03/11 12:43 [pubmed]
PHST- 2024/03/11 08:23 [entrez]
PHST- 2024/03/11 00:00 [pmc-release]
AID - 2323768 [pii]
AID - 10.1080/15384047.2024.2323768 [doi]
PST - ppublish
SO  - Cancer Biol Ther. 2024 Dec 31;25(1):2323768. doi: 10.1080/15384047.2024.2323768. 
      Epub 2024 Mar 11.