Dataset Information

LncRNA CANT1 suppresses retinoblastoma progression by repellinghistone methyltransferase in PI3K? promoter.

ABSTRACT: 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 (PI3K?) and blocked histone methyltransferase hSET1 from binding to the PI3K? promoter, thus abolishing hSET1-mediated histone H3K4 trimethylation of the PI3K? promoter and inhibiting PI3K? expression. Furthermore, we found that silencing PI3K? either by lncRNA CANT1 overexpression or by PI3K? 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.

SUBMITTER: Ni H

PROVIDER: S-EPMC7198571 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

LncRNA CANT1 suppresses retinoblastoma progression by repellinghistone methyltransferase in PI3Kγ promoter.

Ni Hongyan H Chai Peiwei P Yu Jie J Xing Yue Y Wang Shaoyun S Fan Jiayan J Ge Shengfang S Wang Yefei Y Jia Renbing R Fan Xianqun X

Cell death & disease 20200504 5

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 ...[more]

PMID: 32366932

Similar Datasets

Project description:Retinoblastoma (RB) is the most common intraocular tumor in childhood. Long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NTAT1) has been reported to be related to RB progression. This study aims to study the molecular mechanism of NEAT1 in regulating cell cycle, proliferation, apoptosis, migration, and invasion in RB. The expression levels of NEAT1 and miR-3619-5p were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression of LIM and SH3 domain protein 1 (LASP1) was measured by western blot. The proliferation of RB cells was analyzed by cell counting kit-8 (CCK-8) and cell colony formation assays. Cell migration and invasion were evaluated by transwell assay. Cell cycle and apoptosis were assessed by flow cytometry analysis. The association between miR-3619-5p and NEAT1 or LASP1 was predicted by starBase 3.0 database and identified by dual-luciferase reporter assay. The effects of NEAT1 knockdown on the tumor growth in vivo were detected by in vivo tumor formation assay. NEAT1 expression was dramatically up-regulated, and miR-3619-5p expression was obviously downregulated in RB tissues and cells compared with control groups. The protein level of LASP1 was obviously increased in RB tissues or cells relative to paracancerous normal tissues or cells, respectively. Functionally, NEAT1 silencing inhibited RB cell migration, invasion, and proliferation, whereas induced cell apoptosis and cell cycle arrest in RB; this phenomenon was partially abolished by miR-3619-5p inhibitor. Mechanistically, NEAT1 acted as a sponge of miR-3619-5p, and miR-3619-5p was associated with LASP1. In addition, NEAT1 knockdown decreased the volume and weight of RB tumor in vivo. Together, NEAT1 silencing repressed cell migration, invasion, and proliferation, whereas induced cell apoptosis and cycle arrest by sponging miR-3619-5p to inhibit LASP1 expression in RB cells. This study may provide a theoretical basis for RB therapy.

Dataset Information

LncRNA CANT1 suppresses retinoblastoma progression by repellinghistone methyltransferase in PI3K? promoter.

Publications

LncRNA CANT1 suppresses retinoblastoma progression by repellinghistone methyltransferase in PI3Kγ promoter.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets