PR-LncRNA signature regulates glioma cell activity through expression of SOX factors

Abstract

Long non-coding RNAs (LncRNAs) have emerged as a relevant class of genome regulators involved in a broad range of biological processes and with important roles in tumor initiation and malignant progression. We have previously identified a p53-regulated tumor suppressor signature of LncRNAs (PR-LncRNAs) in colorectal cancer. Our aim was to identify the expression and function of this signature in gliomas. We found that the expression of the four PR-LncRNAs tested was high in human low-grade glioma samples and diminished with increasing grade of disease, being the lowest in glioblastoma samples. Functional assays demonstrated that PR-LncRNA silencing increased glioma cell proliferation and oncosphere formation. Mechanistically, we found an inverse correlation between PR-LncRNA expression and SOX1, SOX2 and SOX9 stem cell factors in human glioma biopsies and in glioma cells in vitro. Moreover, knock-down of SOX activity abolished the effect of PR-LncRNA silencing in glioma cell activity. In conclusion, our results demonstrate that the expression and function of PR-LncRNAs are significantly altered in gliomagenesis and that their activity is mediated by SOX factors. These results may provide important insights into the mechanisms responsible for glioblastoma pathogenesis.

A novel ferroptosis-related lncRNA signature for prognosis prediction in gastric cancer

“…Increasing studies have shown that lncRNAs play a crucial role in tumor progression [ 11 , 12 ]. Recently, molecular risk signatures as prognostic predictors of cancer progression were investigated, especially lncRNA signatures [ 13 , 14 ]. However, the prognostic value of ferroptosis-related lncRNAs signature in GC has not been systematically explored.…”

LncRNA HOXA‐AS3 promotes the malignancy of glioblastoma through regulating miR‐455‐5p/USP3 axis

“…LncRNAs regulate tumorigenesis and invasion by activating or silencing oncogenes via various mechanisms, such as epigenetic regulation, RNA decay and post‐translational modification 8 . Many lncRNAs have high levels of expression in brain tumours such as GBM and astrocytoma, and these lncRNAs have been shown to rely on various molecular mechanisms 9 …”

“…8 Many lncRNAs have high levels of expression in brain tumours such as GBM and astrocytoma, and these lncRNAs have been shown to rely on various molecular mechanisms. 9 In the current study, we identified a novel lncRNA, HOXA cluster antisense RNA 3 (HOXA-AS3). It was found to be one of the most up-regulated lncRNAs in GBM tissues.…”

Evolving Landscape of Long Non-coding RNAs in Cerebrospinal Fluid: A Key Role From Diagnosis to Therapy in Brain Tumors

“…In vitro experiments of glioma tissues and cell lines revealed that PR-lncRNA expression was negatively correlated with SOX1, SOX2, and SOX9 stem cell factors. Knockdown of SOX abolished the role of PR-lncRNA silencing in glioma cell activity, indicating that the expression and function of PR-lncRNA were significantly altered in LGG formation ( Torres-Bayona et al, 2018 ). LncRNA H19 can enhance tumorigenesis by directly inducing the c-Myc oncogene ( Barsyte-Lovejoy et al, 2006 ).…”