Abstract
BackgroundAs a newfound type of non-coding RNA, circular RNAs (circRNAs) are involved in various physiological and pathological processes via regulation of gene expression. Increasing evidence shows that aberrantly expressed circRNAs play a crucial role in the initiation and progression of many tumors. However, the functions of different circRNAs in gliomas remain elusive.MethodsThe levels of circRNAs, miRNAs, and mRNAs were quantified by qPCR. The interaction between circDENND2A and miR-625-5p was determined by luciferase reporter and pull-down assays. The migratory and invasive capabilities of glioma cells were examined by wound healing and Transwell assays. Immunohistochemistry was performed to analyze the HIF1α level in glioma tissues.ResultsWe predicted circDENND2A (has_circ_0002142) to be a hypoxia-responsive circRNA in glioma via a bioinformatic analysis. We found that hypoxia induced the expression of circDENND2A, which promoted migration and invasion of glioma cells. To understand the behaviors of circDENND2A in glioma, we studied the putative miRNAs targeted by circDENND2A and identified circDENND2A as an efficient sponge of miR-625-5p in glioma cells. Phenotype experiments verified that circDENND2A was required for the hypoxia-induced migration and invasion of glioma cells and that this occurred by sponging of miR-625-5p. Notably, glioma tissues overexpressing HIF1α exhibited a high expression of circDENND2A as well as a low expression of miR-625-5p. circDENND2A was negatively correlated with miR-625-5p.ConclusioncircDENND2A is required for the hypoxia-induced malignancy of glioma cells and functions by sponging miR-625-5p.
Highlights
Glioma is the most prevalent and malignant tumor of the central nervous system, originating from glial cells [1]
CircCENND2A is a hypoxia-responsive Circular RNA (circRNA) in glioma cells In order to profile the hypoxia-associated circRNAs, we compared the differentially expressed circRNA profiles between glioma and normal tissues (GSE86202) [21] with the differentially expressed mRNA profiles in U87MG cells between hypoxia and normoxia (GSE45301) [22]
To identify the circRNAs involved in response to hypoxia, we examined the levels of the 12 circRNAs in hypoxic or normoxic U87MG cells
Summary
Glioma is the most prevalent and malignant tumor of the central nervous system, originating from glial cells [1]. Su et al Cellular & Molecular Biology Letters (2019) 24:24 polyadenylated tail [4] Their circular structure confers strong resistance to RNase R and a stable existence in cells [5]. Increasing evidence suggests that circRNAs participate in a variety of physiological and pathological processes [9]. As critical regulators in the development and progression of several malignancies, dysregulated circRNAs promote tumor proliferation, migration, and invasion [10,11,12]. As a newfound type of non-coding RNA, circular RNAs (circRNAs) are involved in various physiological and pathological processes via regulation of gene expression. Increasing evidence shows that aberrantly expressed circRNAs play a crucial role in the initiation and progression of many tumors. The functions of different circRNAs in gliomas remain elusive
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