LncRNA CANT1 suppresses retinoblastoma progression by repellinghistone methyltransferase in PI3Kγ promoter
Open Access
- 4 May 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cell Death & Disease
- Vol. 11 (5), 1-15
- https://doi.org/10.1038/s41419-020-2524-y
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 gamma) and blocked histone methyltransferase hSET1 from binding to the PI3K gamma promoter, thus abolishing hSET1-mediated histone H3K4 trimethylation of the PI3K gamma promoter and inhibiting PI3K gamma expression. Furthermore, we found that silencing PI3K gamma either by lncRNA CANT1 overexpression or by PI3K gamma 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.Funding Information
- The Science and Technology Commission of Shanghai
- National Natural Science Foundation of China (81772875, 81770961, U1932135)
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