LncRNA CANT1 suppresses retinoblastoma progression by repellinghistone methyltransferase in PI3Kγ promoter.
Carcinogenesis
/ genetics
Cell Line
Class Ib Phosphatidylinositol 3-Kinase
/ metabolism
Disease Progression
Down-Regulation
/ genetics
Gene Expression Regulation, Neoplastic
Histone-Lysine N-Methyltransferase
/ metabolism
Histones
/ metabolism
Humans
Lysine
/ metabolism
Methylation
Promoter Regions, Genetic
Protein Binding
Proto-Oncogene Proteins c-akt
/ metabolism
RNA, Long Noncoding
/ genetics
Retinoblastoma
/ genetics
Signal Transduction
Transcription, Genetic
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
04 05 2020
04 05 2020
Historique:
received:
07
01
2020
accepted:
14
04
2020
revised:
12
04
2020
entrez:
6
5
2020
pubmed:
6
5
2020
medline:
23
3
2021
Statut:
epublish
Résumé
Retinoblastoma (RB) is the most common malignant intraocular tumor of childhood. Recent studies have shown that long noncoding RNAs (lncRNAs), which are longer than 200 bp and without protein-coding ability, are key regulators of tumorigenesis. However, the role of lncRNAs in retinoblastoma remains to be elucidated. In this study, we found that the expression of lncRNA CASC15-New-Transcript 1 (CANT1) was significantly downregulated in RB. Notably, overexpression of CANT1 significantly inhibited RB growth both in vitro and in vivo. Furthermore, lncRNA CANT1, which was mainly located in the nucleus, occupied the promoter of phosphoinositide 3-kinase gamma (PI3Kγ) and blocked histone methyltransferase hSET1 from binding to the PI3Kγ promoter, thus abolishing hSET1-mediated histone H3K4 trimethylation of the PI3Kγ promoter and inhibiting PI3Kγ expression. Furthermore, we found that silencing PI3Kγ either by lncRNA CANT1 overexpression or by PI3Kγ siRNA, reduced the activity of PI3K/Akt signaling and suppressed RB tumorigenesis. In summary, lncRNA CANT1 acts as a suppressor of RB progression by blocking gene-specific histone methyltransferase recruitment. These findings outline a new CANT1 modulation mechanism and provide an alternative option for the RB treatment.
Identifiants
pubmed: 32366932
doi: 10.1038/s41419-020-2524-y
pii: 10.1038/s41419-020-2524-y
pmc: PMC7198571
doi:
Substances chimiques
Histones
0
RNA, Long Noncoding
0
Histone-Lysine N-Methyltransferase
EC 2.1.1.43
Setd1A protein, human
EC 2.1.1.43
Class Ib Phosphatidylinositol 3-Kinase
EC 2.7.1.137
PIK3CG protein, human
EC 2.7.1.137
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Lysine
K3Z4F929H6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
306Références
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