Divergent lncRNA MYMLR regulates MYC by eliciting DNA looping and promoter-enhancer interaction.
A549 Cells
Animals
Cell Cycle
Cell Line, Tumor
Cell Proliferation
Down-Regulation
Enhancer Elements, Genetic
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms
/ genetics
Mice
Neoplasm Transplantation
Proteomics
Proto-Oncogene Proteins c-myc
/ genetics
RNA, Long Noncoding
/ genetics
RNA-Binding Proteins
/ genetics
Systems Biology
MYC
enhancer
lncRNA
lung cancer
systems biology
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
02 09 2019
02 09 2019
Historique:
received:
17
10
2017
revised:
13
06
2019
accepted:
21
06
2019
pubmed:
31
7
2019
medline:
24
12
2019
entrez:
31
7
2019
Statut:
ppublish
Résumé
Long non-coding RNAs (lncRNAs) function in a wide range of processes by diverse mechanisms, though their roles in regulation of oncogenes and/or tumor suppressors remain rather elusive. We performed a global search for lncRNAs affecting MYC activity using a systems biology-based approach with a K supercomputer and the GIMLET algorism based on local distance correlations. Consequently, MYMLR was identified and experimentally shown to maintain MYC transcriptional activity and cell cycle progression despite the low levels of expression. A proteomic search for MYMLR-binding proteins identified PCBP2, while it was also found that MYMLR places a 557-kb upstream enhancer region in the proximity of the MYC promoter in cooperation with PCBP2. These findings implicate a crucial role for MYMLR in regulation of the archetypical oncogene MYC and warrant future studies regarding the involvement of low copy number lncRNAs in regulation of other crucial oncogenes and tumor suppressor genes.
Identifiants
pubmed: 31361039
doi: 10.15252/embj.201798441
pmc: PMC6717891
doi:
Substances chimiques
MYC protein, human
0
PCBP2 protein, human
0
Proto-Oncogene Proteins c-myc
0
RNA, Long Noncoding
0
RNA-Binding Proteins
0
long noncoding RNA CASC11, human
0
Banques de données
GEO
['GSE103085']
GENBANK
['MH782193']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e98441Subventions
Organisme : Ministry of Education, Culture, Sports, Science and Technology (MEXT)
ID : 15H05910
Pays : International
Organisme : MEXT|Japan Society for the Promotion of Science (JSPS)
ID : 16H02468
Pays : International
Organisme : MEXT|Japan Society for the Promotion of Science (JSPS)
ID : 16K19050
Pays : International
Organisme : Princess Takamatsu Cancer Research Fund
Pays : International
Organisme : Japan Agency for Medical Research and Development (AMED)
ID : 18ck0106363h0002
Pays : International
Informations de copyright
© 2019 The Authors.
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