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PR-LncRNA 特征通过 SOX 因子表达调控神经胶质瘤细胞活性。

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

机构信息

Donostia University Hospital, San Sebastian, Spain.

Cellular Oncology group, Biodonostia Institute, San Sebastian, Spain.

出版信息

Sci Rep. 2018 Aug 24;8(1):12746. doi: 10.1038/s41598-018-30836-5.

DOI:10.1038/s41598-018-30836-5
PMID:30143669
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6109087/
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.

摘要

长非编码 RNA（lncRNAs）已成为一类相关的基因组调控因子，参与广泛的生物学过程，并在肿瘤起始和恶性进展中发挥重要作用。我们之前在结直肠癌中鉴定了一个受 p53 调控的肿瘤抑制 lncRNA （PR-LncRNAs）特征。我们的目的是鉴定该特征在神经胶质瘤中的表达和功能。我们发现，在人类低级别神经胶质瘤样本中，四种测试的 PR-LncRNAs 的表达较高，随着疾病级别的增加而降低，在神经胶质母细胞瘤样本中表达最低。功能测定表明，PR-LncRNA 沉默增加了神经胶质瘤细胞的增殖和肿瘤球形成。从机制上讲，我们在人类神经胶质瘤活检和体外神经胶质瘤细胞中发现 PR-LncRNA 表达与 SOX1、SOX2 和 SOX9 干细胞因子之间存在反比相关性。此外，SOX 活性的敲低消除了 PR-LncRNA 沉默对神经胶质瘤细胞活性的影响。总之，我们的结果表明，PR-LncRNAs 的表达和功能在神经胶质瘤发生中发生了显著改变，其活性由 SOX 因子介导。这些结果可能为胶质母细胞瘤发病机制的研究提供重要的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2882/6109087/ab6db424e777/41598_2018_30836_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2882/6109087/974da5df0e02/41598_2018_30836_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2882/6109087/f95d6f0c355c/41598_2018_30836_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2882/6109087/0b1f94589c60/41598_2018_30836_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2882/6109087/ab6db424e777/41598_2018_30836_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2882/6109087/974da5df0e02/41598_2018_30836_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2882/6109087/f95d6f0c355c/41598_2018_30836_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2882/6109087/0b1f94589c60/41598_2018_30836_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2882/6109087/ab6db424e777/41598_2018_30836_Fig4_HTML.jpg

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