YY1‐mediated up‐regulation of lncRNA LINC00466 facilitates glioma progression via miR‐508/CHEK1. (24th November 2020)

• Record Type: Journal Article
• Authors: Li, Fei; Shen, Zheng‐Ze; Xiao, Chao‐Ming; Sha, Qian‐Kun
• Is Part Of: Journal of gene medicine. Volume 23:Number 1(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-11-24
• Subjects: biomarker -- CHEK1 -- glioma -- LINC00466 -- metastasis -- miR‐508 -- therapeutic target; Genetic transformation -- Periodicals; Gene Transfer -- Periodicals; Gene Therapy -- Periodicals; 616.042
• DOI: 10.1002/jgm.3287
• Languages: English
• ISSNs: 1099-498X

Abstract

Abstract: Background: The abnormal expression of lncRNA LINC00466 (LINC00466) has been demonstrated in several tumor types. However, the expression pattern and functions of LINC00466 in glioma remain uninvestigated. Methods: A reverse transcriptase‐polymerase chain reaction (RT‐PCR) was utilized to analyze LINC00466 in human glioma tissues and cell lines. Luciferase reporter assays were performed to explore whether YY1 could bind to the promoter region of LINC00466. Cell counting kit‐8, flow cytometry, colony‐formation, transwell migration and invasion assays were carried out to determine the involvement of INC00466 in glioma. Luciferase assays and pulldown assays were conducted to verify the binding sites. Results: We report that LINC00466 expression is increased in glioma cells and tissues. YY1 transcription factor (YY1) can bind directly to the LINC00466 promoter region. Clinical studies revealed that the elevated expression of LINC00466 is closely correlated with an advanced World Health Organization grade ( p = 0.008), Karnofsky Performance Status score ( p = 0.004) and a short overall survival ( p = 0.0035) of glioma patients. Functional assays revealed that LINC00466 knockdown distinctly suppresses glioma cell proliferation, migration, invasion and epithelial–mesenchymal progress, and also promotes apoptosis. Moreover, dual‐luciferase reporter assays indicated that LINC00466 acts as an endogenous sponge via binding to miR‐508 and decreasing its expression. Luciferase assays and RT‐PCR assays demonstrated that checkpoint kinase 1 (CHEK1) is a target of miR‐508, and LINC00466 modulates CHEK1 levels by competing for miR‐508. LINC00466 may exhibit its anti‐oncogenic roles through targeting the miR‐508/CHEK1 axis. Conclusions: Our findings identified a novel glioma‐related long non‐coding RNA, LINC00466, which may provide a potential novel prognostic and therapeutic target for glioma. Abstract : YY1‐mediated up‐regulation of long non‐coding RNA LINC00466 functions as a competing endogenous RNA for miR‐508 to facilitate glioma progression through the regulation of CHEK1.