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

Autor: Jing Wu, Xiaoxue Sun, Lijie Sheng, Duo Dong, Xuewu Gong
Rok vydání: 2018
Předmět:
Zdroj: Gene. 668
ISSN: 1879-0038
Popis: 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.
Databáze: OpenAIRE
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