SP1-induced upregulation of lncRNA PANDAR predicts adverse phenotypes in retinoblastoma and regulates cell growth and apoptosis in vitro and in vivo

SP1-induced upregulation of lncRNA PANDAR predicts adverse phenotypes in retinoblastoma and... Retinoblastoma (RB) is an intraocular malignancy for children and has a high mortality rate. Long non-coding RNAs (lncRNAs) are emerging as gene regulators and biomarkers in various malignancies. PANDAR is a novel cancer-related lncRNA that dysregulated in several types of cancers. However, its clinical value and potential effects on RB remains unclear. RT-qPCR was used to assess the relative expression of PANDAR in RB tissues and cells. Additionally, chromatin immunoprecipitation (ChIP) and luciferase reporter assays were performed to investigate whether SP1 could bind to the promoter region of PANDAR and activate its transcription. Furthermore, in vitro and in vivo studies were induced to elucidate the biological functions of PANDAR. The results indicated that PANDAR was increased in RB tissues and cells, and this upregulation was associated with advanced IIRC stage, positive optic nerve invasion, and lower differentiation grade in RB patients. In addition, SP1 could bind directly to the PANDAR promoter region and activate its transcription. Furthermore, PANDAR silencing yielded tumor suppressive effects both in vitro and in vivo. Importantly, PANDAR protects against apoptosis partly by affecting Bcl-2/caspase-3 pathway. Ultimately, our work first illustrate that PANDAR plays an oncogenic role in RB and may offer a potential therapeutic target for treating this devastating disease. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Gene Elsevier

SP1-induced upregulation of lncRNA PANDAR predicts adverse phenotypes in retinoblastoma and regulates cell growth and apoptosis in vitro and in vivo

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Publisher
Elsevier
Copyright
Copyright © 2018 Elsevier B.V.
ISSN
0378-1119
eISSN
1879-0038
D.O.I.
10.1016/j.gene.2018.05.065
Publisher site
See Article on Publisher Site

Abstract

Retinoblastoma (RB) is an intraocular malignancy for children and has a high mortality rate. Long non-coding RNAs (lncRNAs) are emerging as gene regulators and biomarkers in various malignancies. PANDAR is a novel cancer-related lncRNA that dysregulated in several types of cancers. However, its clinical value and potential effects on RB remains unclear. RT-qPCR was used to assess the relative expression of PANDAR in RB tissues and cells. Additionally, chromatin immunoprecipitation (ChIP) and luciferase reporter assays were performed to investigate whether SP1 could bind to the promoter region of PANDAR and activate its transcription. Furthermore, in vitro and in vivo studies were induced to elucidate the biological functions of PANDAR. The results indicated that PANDAR was increased in RB tissues and cells, and this upregulation was associated with advanced IIRC stage, positive optic nerve invasion, and lower differentiation grade in RB patients. In addition, SP1 could bind directly to the PANDAR promoter region and activate its transcription. Furthermore, PANDAR silencing yielded tumor suppressive effects both in vitro and in vivo. Importantly, PANDAR protects against apoptosis partly by affecting Bcl-2/caspase-3 pathway. Ultimately, our work first illustrate that PANDAR plays an oncogenic role in RB and may offer a potential therapeutic target for treating this devastating disease.

Journal

GeneElsevier

Published: Aug 20, 2018

References

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