Long non-coding RNA NCK1-AS1 promotes the tumorigenesis of glioma through sponging microRNA-138-2-3p and activating the TRIM24/Wnt/β-catenin axis

• Main Authors: Lifa Huang, Xu Li, Hui Ye, Yajun Liu, Xiaolong Liang, Chao Yang, Lin Hua, Zhaoxian Yan, Xin Zhang
• Format: Article
• Language: English
• Published: BMC 2020-04-01
• Series: Journal of Experimental & Clinical Cancer Research
• Subjects: Long non-coding RNA NCK1-AS1; microRNA-138-2-3p; TRIM24; Wnt/β-catenin signaling pathway; Glioma
• Online Access: http://link.springer.com/article/10.1186/s13046-020-01567-1

Abstract Background Glioma 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. Methods Microarray 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. Results High 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. Conclusions Our 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.