Abstract
Glioma is the most prevalent tumor of the central nervous system. To identify differentially expressed miRNAs (DEMs) in gliomas of different grades, bioinformatics analysis was performed. The DEMs between low-grade gliomas (LGGs) and high-grade gliomas (HGGs) were identified by screening the Gene Expression Omnibus and The Cancer Genome Atlas databases using the LIMMA package. Six overlapping DEMs were identified by comparing LGGs and HGGs. Downregulation of miR-1298-3p correlated with poor overall survival rates in glioma patients. Overexpression of miR-1298-3p induced apoptosis of glioma cells and inhibited glioma cell proliferation, migration, and invasion. The basement membrane protein Nidogen-1 (NID1) was identified as a direct binding target of miR-1298-3p in glioma cells. MiR-1298-3p agonist downregulated the NID1 and vimentin levels, but upregulated the level of E-cadherin in glioma cells. Importantly, overexpression of miR-1298-3p induced apoptosis and reduced tumor growth in a mouse xenograft model of glioma. Our results show that miR-1298-3p functions as a tumor suppressor in glioma cells, and suggest that it might serve as a potential biomarker and therapeutic target in glioma patients.
Highlights
Glioma is the most prevalent type of cancer of the central nervous system, and accounts for about 80% of malignant brain tumors [1, 2]
Glioma miRNAs expression dataset was downloaded from the the Cancer Genome Atlas (TCGA) database, and miRNA profile was analyzed using the LIMMA package for low-grade gliomas (LGGs) and high-grade gliomas (HGGs)
A total of 147 differentially expressed miRNAs (DEMs) were identified in the GSE42657 dataset (Figure 1A), and 25 DEMs were identified in the TCGA dataset (Figure 1B)
Summary
Glioma is the most prevalent type of cancer of the central nervous system, and accounts for about 80% of malignant brain tumors [1, 2]. Glioma is characterized by a rapid cell proliferation, aggressive invasion, and a poor prognosis [3, 4]. GBM is the most aggressive brain tumor with an extremely poor prognosis [7]. MiRNAs regulate gene expression by directly targeting the 3′-untranslated regions (3′-UTRs) of target mRNAs [12]. MiRNAs can silence gene expression by inhibiting translation initiation and inducing degradation of target mRNAs [13]. MiRNAs are involved in different physiological processes, such as cell proliferation, apoptosis, differentiation, metastasis, and tumorigenesis [14]. Recent studies have suggested that miRNAs are involved in glioma tumorigenesis by functioning as oncogenes or tumor suppressors, and might serve as diagnostic and prognostic glioma biomarkers [15, 16]
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