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Genome-Wide Microarray Analysis of circRNAs Revealed Novel Biomarkers for Glioma Treatment and Their Promoting Effect on Glioma Progression.

ABSTRACT: Purpose:As a novel type of non-coding RNAs, circRNAs were found to play important roles in cancer progression. In this study, we aim to investigate genome-wide circRNAs expression and potential functions in glioma to find new therapeutic targets for glioma treatment. Patients and Methods:A total of 92 pairs of glioma tissue samples and adjacent control samples were enrolled in this study. Microarray and bioinformatics tools were used to identify circRNAs expression in glioma. Relative expression of RNAs was validated by qRT-PCR. Cell viability and migration were measured by Cell Counting Kit-8 and wound-healing assay in U251 and SHG-44 cells. The statistical correlation and overall survival were calculated by Mann-Whitney U-test and Kaplan-Meier method. Results:A total of 90 differentially expressed circRNAs were identified in glioma tissues compared to control. These circRNAs were mainly back-spliced forms chr1, chr6 and chr12 with a variable number of exons. QRT-PCR showed hsa_circ_0013520 and hsa_circ_0004379 were highly expressed in glioma tissues and cell lines. High expression of hsa_circ_0013520 and hsa_circ_0004379 was significantly correlated with tumor size (P-value < 0.001), Karnofsky Performance Status (KPS, P-value: 0.008 and 0.006) and TNM stage (P-value: 0.004 and 0.005). Moreover, patients with higher expression level of hsa_circ_0013520 and hsa_circ_0004379 had a poorer overall survival (P-value: < 0.01). Besides, loss-of-function experiments revealed that inhibition of hsa_circ_0013520 and hsa_circ_0004379 suppresses proliferation and invasion of glioma cells. Conclusion:The present study is the first to report that hsa_circ_0013520 and hsa_circ_0004379 were up-regulated in glioma tissues and cell lines, and their expression was positively correlated with poor clinical features of glioma patients, which may serve as novel biomarkers for glioma diagnosis and therapy.

SUBMITTER: Lyu X

PROVIDER: S-EPMC7136664 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Genome-Wide Microarray Analysis of circRNAs Revealed Novel Biomarkers for Glioma Treatment and Their Promoting Effect on Glioma Progression.

Lyu Xiaojuan X Zhou Lin L Fan Fengjuan F Dong Zhen Z

OncoTargets and therapy 20200401

<h4>Purpose</h4>As a novel type of non-coding RNAs, circRNAs were found to play important roles in cancer progression. In this study, we aim to investigate genome-wide circRNAs expression and potential functions in glioma to find new therapeutic targets for glioma treatment.<h4>Patients and methods</h4>A total of 92 pairs of glioma tissue samples and adjacent control samples were enrolled in this study. Microarray and bioinformatics tools were used to identify circRNAs expression in glioma. Rela ...[more]

PMID: 32308410

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Project description:BackgroundGlioblastoma, the most common primary malignant tumor of the brain, is associated with poor prognosis. Glioblastoma cells exhibit high proliferative and invasive properties, and glioblastoma stem cells (GSCs) have been shown to play a crucial role in the malignant behavior of glioblastoma cells. This study aims to investigate the molecular mechanisms involved in GSCs maintenance and malignant progression.MethodsBioinformatics analysis was performed based on data from public databases to explore the expression profile of Mitotic arrest deficient 2 like 2 (MAD2L2) and its potential function in glioma. The impact of MAD2L2 on glioblastoma cell behaviors was assessed through cell viability assays (CCK8), colony formation assays, 5-Ethynyl-2'-deoxyuridine (EDU) incorporation assays, scratch assays, and transwell migration/invasion assays. The findings from in vitro experiments were further validated in vivo using xenograft tumor model. GSCs were isolated from the U87 and LN229 cell lines through flow cytometry and the stemness characteristics were verified by immunofluorescence staining. The sphere-forming ability of GSCs was examined using the stem cell sphere formation assay. Bioinformatics methods were conducted to identified the potential downstream target genes of MAD2L2, followed by in vitro experimental validation. Furthermore, potential upstream transcription factors that regulate MAD2L2 expression were confirmed through chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays.ResultsThe MAD2L2 exhibited high expression in glioblastoma samples and showed significant correlation with patient prognosis. In vitro and in vivo experiments confirmed that silencing of MAD2L2 led to decreased proliferation, invasion, and migration capabilities of glioblastoma cells, while decreasing stemness characteristics of glioblastoma stem cells. Conversely, overexpression of MAD2L2 enhanced these malignant behaviors. Further investigation revealed that MYC proto-oncogene (c-MYC) mediated the functional role of MAD2L2 in glioblastoma, which was further validated through a rescue experiment. Moreover, using dual-luciferase reporter gene assays and ChIP assays determined that the upstream transcription factor E2F-1 regulated the expression of MAD2L2.ConclusionOur study elucidated the role of MAD2L2 in maintaining glioblastoma stemness and promoting malignant behaviors through the regulation of c-MYC, suggesting its potential as a therapeutic target.

Dataset Information

Genome-Wide Microarray Analysis of circRNAs Revealed Novel Biomarkers for Glioma Treatment and Their Promoting Effect on Glioma Progression.

Publications

Genome-Wide Microarray Analysis of circRNAs Revealed Novel Biomarkers for Glioma Treatment and Their Promoting Effect on Glioma Progression.

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