PMID- 34765312
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211113
IS  - 2156-6976 (Print)
IS  - 2156-6976 (Electronic)
IS  - 2156-6976 (Linking)
VI  - 11
IP  - 10
DP  - 2021
TI  - The transcription co-factor JAB1/COPS5, serves as a potential oncogenic hub of 
      human chondrosarcoma cells in vitro.
PG  - 5063-5075
AB  - Chondrosarcoma (CS) is the second most common skeletal malignancy in humans. 
      High-grade CS is aggressive and extremely resistant to chemo- and 
      radio-therapies. The lack of effective treatment options warrants the development 
      of novel therapies. The evolutionarily conserved transcriptional co-factor JAB1 
      (also known as COPS5/CSN5) has emerged as a novel regulator of tumorigenesis. 
      JAB1 overexpression occurs in many common cancers and is associated with poor 
      prognosis. However, the role of JAB1 in CS pathogenesis was completely unknown. 
      To study JAB1's function in CS, we performed shRNA knockdown (KD) of JAB1 in two 
      high-grade human CS cell lines, SW1353 and Hs819.T, and observed significantly 
      decreased proliferation and colony formations, and increased apoptosis in both CS 
      cell lines upon JAB1-KD. Interestingly, we found that endogenous JAB1 interacted 
      with endogenous SOX9, a potent oncogene and a master regulator of skeletogenesis, 
      in chondrosarcoma cells, but not in primary chondrocytes. JAB1 also binds to the 
      same SOX9-mediated chondrocyte-specific enhancer elements in CS cells. 
      Furthermore, we found that a recently developed, novel, potent, and JAB1-specific 
      small molecule inhibitor, CSN5i-3, can significantly increase apoptosis, 
      drastically alter the activities of several signaling pathways, and modulates the 
      expression of specific Cullin-ring-ligases (CRLs) in CS cells. Finally, our 
      RNA-sequencing analysis in JAB1-KD CS cells identified a total of 2945 
      differentially expressed genes. Gene set enrichment analysis revealed that JAB1 
      regulates several essential pathways such as DNA damage response and cell cycle 
      regulation. In conclusion, our study showed that JAB1 might regulate a distinct 
      pro-tumorigenic regulatory network to promote chondrosarcoma pathogenesis.
CI  - AJCR Copyright (c) 2021.
FAU - Mamidi, Murali K
AU  - Mamidi MK
AD  - Department of Orthopaedics, Case Western Reserve University, Biomedical Research 
      Building #328, 2109 Adelbert Road, Cleveland, OH 44106, USA.
AD  - Case Comprehensive Cancer Cancer, Case Western Reserve University, Biomedical 
      Research Building #328, 2109 Adelbert Road, Cleveland, OH 44106, USA.
AD  - Stephenson Cancer Center, University of Oklahoma Health Sciences Center Oklahoma, 
      USA.
FAU - Samsa, William E
AU  - Samsa WE
AD  - Department of Orthopaedics, Case Western Reserve University, Biomedical Research 
      Building #328, 2109 Adelbert Road, Cleveland, OH 44106, USA.
AD  - Case Comprehensive Cancer Cancer, Case Western Reserve University, Biomedical 
      Research Building #328, 2109 Adelbert Road, Cleveland, OH 44106, USA.
FAU - Danielpour, David
AU  - Danielpour D
AD  - Case Comprehensive Cancer Cancer, Case Western Reserve University, Biomedical 
      Research Building #328, 2109 Adelbert Road, Cleveland, OH 44106, USA.
AD  - Division of General Medical Sciences, Case Western Reserve University, Biomedical 
      Research Building #328, 2109 Adelbert Road, Cleveland, OH 44106, USA.
FAU - Chan, Ricky
AU  - Chan R
AD  - Institute for Computational Biology, Case Western Reserve University, Biomedical 
      Research Building #328, 2109 Adelbert Road, Cleveland, OH 44106, USA.
FAU - Zhou, Guang
AU  - Zhou G
AD  - Department of Orthopaedics, Case Western Reserve University, Biomedical Research 
      Building #328, 2109 Adelbert Road, Cleveland, OH 44106, USA.
AD  - Case Comprehensive Cancer Cancer, Case Western Reserve University, Biomedical 
      Research Building #328, 2109 Adelbert Road, Cleveland, OH 44106, USA.
AD  - Department of Genetics and Genome Sciences, Case Western Reserve University, 
      Biomedical Research Building #328, 2109 Adelbert Road, Cleveland, OH 44106, USA.
LA  - eng
PT  - Journal Article
DEP - 20211015
PL  - United States
TA  - Am J Cancer Res
JT  - American journal of cancer research
JID - 101549944
PMC - PMC8569363
OTO - NOTNLM
OT  - COP9 signalosome
OT  - JAB1/COPS5
OT  - SOX9
OT  - chondrosarcoma
OT  - transcriptome
COIS- None.
EDAT- 2021/11/13 06:00
MHDA- 2021/11/13 06:01
PMCR- 2021/10/15
CRDT- 2021/11/12 07:04
PHST- 2019/11/11 00:00 [received]
PHST- 2021/06/07 00:00 [accepted]
PHST- 2021/11/12 07:04 [entrez]
PHST- 2021/11/13 06:00 [pubmed]
PHST- 2021/11/13 06:01 [medline]
PHST- 2021/10/15 00:00 [pmc-release]
PST - epublish
SO  - Am J Cancer Res. 2021 Oct 15;11(10):5063-5075. eCollection 2021.