PMID- 32721119
OWN - NLM
STAT- MEDLINE
DCOM- 20211004
LR  - 20211004
IS  - 2573-8348 (Electronic)
IS  - 2573-8348 (Linking)
VI  - 2
IP  - 5
DP  - 2019 Oct
TI  - Tumorigenic effects of TLX overexpression in HEK 293T cells.
PG  - e1204
LID - 10.1002/cnr2.1204 [doi]
LID - e1204
AB  - BACKGROUND: The human orphan receptor TLX (NR2E1) is a key regulator of 
      neurogenesis, adult stem cell maintenance, and tumorigenesis. However, little is 
      known about the genetic and transcriptomic events that occur following TLX 
      overexpression in human cell lines. AIMS: Here, we used cytogenetics and RNA 
      sequencing to investigate the effect of TLX overexpression with an inducible 
      vector system in the HEK 293T cell line. METHODS AND RESULTS: Conventional 
      spectral karyotyping was used to identify chromosomal abnormalities, followed by 
      fluorescence in situ hybridization (FISH) analysis on chromosome spreads to 
      assess TLX DNA copy number. Illumina paired-end whole transcriptome sequencing 
      was then performed to characterize recurrent genetic variants (single nucleotide 
      polymorphisms (SNPs) and indels), expressed gene fusions, and gene expression 
      profiles. Lastly, flow cytometry was used to analyze cell cycle distribution. 
      Intriguingly, we show that upon transfection with a vector containing the human 
      TLX gene (eGFP-hTLX), an isochromosome forms on the long arm of chromosome 6, 
      thereby resulting in DNA gain of the TLX locus (6q21) and upregulation of TLX. 
      Induction of the eGFP-hTLX vector further increased TLX expression levels, 
      leading to G0-G1 cell cycle arrest, genetic aberrations, modulation of gene 
      expression patterns, and crosstalk with other nuclear receptors (AR, ESR1, ESR2, 
      NR1H4, and NR3C2). We identified a 49-gene signature associated with central 
      nervous system (CNS) development and carcinogenesis, in addition to potentially 
      cancer-driving gene fusions (LARP1-CNOT8 and NSL1-ZDBF2) and deleterious genetic 
      variants (frameshift insertions in the CTSH, DBF4, POSTN, and WDR78 genes). 
      CONCLUSION: Taken together, these findings illustrate that TLX may play a pivotal 
      role in tumorigenesis via genomic instability and perturbation of cancer-related 
      processes.
CI  - (c) 2019 Wiley Periodicals, Inc.
FAU - Parris, Toshima Z
AU  - Parris TZ
AUID- ORCID: 0000-0003-0834-5540
AD  - Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Cancer 
      Center, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
FAU - Vizlin-Hodzic, Dzeneta
AU  - Vizlin-Hodzic D
AD  - Department of Psychiatry and Neurochemistry, Institute of Neuroscience and 
      Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
AD  - Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska 
      Academy at University of Gothenburg, Gothenburg, Sweden.
FAU - Salmela, Susanne
AU  - Salmela S
AD  - Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, 
      Sahlgrenska Cancer Center, Sahlgrenska Academy at University of Gothenburg, 
      Gothenburg, Sweden.
FAU - Funa, Keiko
AU  - Funa K
AD  - Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, 
      Sahlgrenska Cancer Center, Sahlgrenska Academy at University of Gothenburg, 
      Gothenburg, Sweden.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190725
PL  - United States
TA  - Cancer Rep (Hoboken)
JT  - Cancer reports (Hoboken, N.J.)
JID - 101747728
RN  - 0 (NR2E1 protein, human)
RN  - 0 (Orphan Nuclear Receptors)
SB  - IM
MH  - Cell Proliferation/genetics
MH  - Cell Transformation, Neoplastic/*genetics
MH  - Frameshift Mutation
MH  - G1 Phase Cell Cycle Checkpoints/genetics
MH  - Gene Expression Regulation, Neoplastic
MH  - *Genomic Instability
MH  - HEK293 Cells
MH  - Humans
MH  - Orphan Nuclear Receptors/genetics/*metabolism
MH  - RNA-Seq
MH  - Up-Regulation
PMC - PMC7941458
OTO - NOTNLM
OT  - NR2E1
OT  - TLX
OT  - cancer
OT  - genome instability
OT  - nuclear receptors
EDAT- 2020/07/29 06:00
MHDA- 2021/10/05 06:00
PMCR- 2019/07/25
CRDT- 2020/07/29 06:00
PHST- 2019/03/20 00:00 [received]
PHST- 2019/05/28 00:00 [revised]
PHST- 2019/06/04 00:00 [accepted]
PHST- 2020/07/29 06:00 [entrez]
PHST- 2020/07/29 06:00 [pubmed]
PHST- 2021/10/05 06:00 [medline]
PHST- 2019/07/25 00:00 [pmc-release]
AID - CNR21204 [pii]
AID - 10.1002/cnr2.1204 [doi]
PST - ppublish
SO  - Cancer Rep (Hoboken). 2019 Oct;2(5):e1204. doi: 10.1002/cnr2.1204. Epub 2019 Jul 
      25.