Abstract
BackgroundGlioma is a common brain malignancy with high mortality. The competing endogenous RNA (ceRNA) networks may play key roles in cancer progression. This study was conducted to probe the role of long noncoding RNA (lncRNA) NCK1-AS1 in glioma progression and the involved mechanisms.MethodsMicroarray analyses were performed to explore the lncRNAs/miRNAs/genes with differential expression in glioma. NCK1-AS1 levels in glioma tissues and normal brain tissues, and in glioma cell lines and normal human glial cells were identified. The interactions among NCK1-AS1, miR-138-2-3p and TRIM24 were validated through luciferase reporter, RNA immunoprecipitation and RNA pull-down assays. Gain- and loss-of functions of NCK1-AS1, miR-138-2-3p and TRIM24 were performed to identify their roles in the behaviors of glioma cells. The activity of the Wnt/β-catenin pathway was measured. In vivo experiments were performed as well.ResultsHigh expression of NCK1-AS1 was found in glioma tissues and cells, especially in U251 cells. Online predictions and the integrated experiments identified that NCK1-AS1 elevated the TRIM24 expression through sponging miR-138-2-3p, and further activated the Wnt/β-catenin pathway. Artificial silencing of NCK1-AS1 or up-regulation of miR-138-2-3p led to inhibited proliferation, invasion and migration but promoted cell apoptosis of U251 cells, while up-regulation of TRIM24 reversed these changes, and it activated the Wnt/β-catenin pathway. The in vitro results were reproduced in in vivo experiments.ConclusionsOur study suggested that NCK1-AS1 might elevate TRIM24 expression and further activate the Wnt/β-catenin pathway via acting as a ceRNA for miR-138-2-3p. Silencing of NCK1-AS1 might inhibit the progression of glioma.
Highlights
Glioma is a common brain malignancy with high mortality
LncRNAs are larger than 200 nucleotides, and their importance in gene expression, key cellular processes, metastasis and disease prognosis in cancer has been largely studied [6, 7], including in glioma [8, 9]. miRNAs are 20–25 nucleotides in length, and they down-regulate gene expression by binding with target mRNAs post-transcriptionally resulting in transcript degradation [10]. miRNAs exert critical functions in fundamental cellular process such as cell proliferation, apoptosis, development and inflammation [11]
NCK1-AS1 is highly expressed in PC tissues Differentially expressed long noncoding RNA (lncRNA) in the glioma microarrays GSE50161 and GSE35493 were analyzed, and the heatmap for top 10 highly expressed lncRNAs in the microarray GSE50161 was produced (Fig. 1a)
Summary
The competing endogenous RNA (ceRNA) networks may play key roles in cancer progression. This study was conducted to probe the role of long noncoding RNA (lncRNA) NCK1-AS1 in glioma progression and the involved mechanisms. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are two large classes of non-protein-coding transcripts that participate in diverse essential cellular processes through multiple mechanisms [4, 5]. LncRNAs are larger than 200 nucleotides, and their importance in gene expression, key cellular processes, metastasis and disease prognosis in cancer has been largely studied [6, 7], including in glioma [8, 9]. Several ceRNA networks have been validated to play key functions in metastasis, proliferation, and apoptosis in human glioma cells [16, 17]. The possible ceRNA networks in glioma and the mechanisms involved remain largely unknown
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