YY1‐mediated up‐regulation of lncRNA LINC00466 facilitates glioma progression via miR‐508/CHEK1

Abstract

BackgroundThe 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.MethodsA 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.ResultsWe 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.ConclusionsOur findings identified a novel glioma‐related long non‐coding RNA, LINC00466, which may provide a potential novel prognostic and therapeutic target for glioma.

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“…Previous studies have reported that the YY1 transcription factor can transcriptionally activate various lncRNAs [34,[38][39][40][41]. Hence, we investigated whether YY1 could regulate LINC02532 expression at the transcriptional level.…”

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PLAU is associated with cell migration and invasion and is regulated by transcription factor YY1 in cervical cancer

“…YinYang1 (YY1), a member of the GLI-Krüppel family of zinc-finger DNA-binding proteins, is a transcription factor widely expressed in various tissues. YY1 can activate the transcription of several target genes, such as FOXE1, TNK2-AS1 and LINC00466 (24)(25)(26). By regulating these target genes,…”