Abstract
BackgroundMicroRNAs (miRNAs) are short, non-coding RNAs that regulate the expression of multiple target genes. Deregulation of miRNAs is common in human tumorigenesis. Low level expression of miR-26b has been found in glioma cells. However, its underlying mechanism of action has not been determined.Methodology/Principal FindingsReal-time PCR was employed to measure the expression level of miR-26b in glioma patients and cells. The level of miR-26b was inversely correlated with the grade of glioma. Ectopic expression of miR-26b inhibited the proliferation, migration and invasion of human glioma cells. A binding site for miR-26b was identified in the 3′UTR of EphA2. Over-expression of miR-26b in glioma cells repressed the endogenous level of EphA2 protein. Vasculogenic mimicry (VM) experiments were performed to further confirm the effects of miR-26b on the regulation of EphA2, and the results showed that miR-26b inhibited the VM processes which regulated by EphA2.SignificanceThis study demonstrated that miR-26b may act as a tumor suppressor in glioma and it directly regulates EphA2 expression. EphA2 is a direct target of miR-26b, and the down-regulation of EphA2 mediated by miR-26b is dependent on the binding of miR-26b to a specific response element of microRNA in the 3′UTR region of EphA2 mRNA.
Highlights
MicroRNAs are short single stranded RNA molecules, which serve as master regulators of gene expression. miRNAs regulate gene expression in a sequence-specific fashion; miRNAs bind to 39untranslated regions (UTRs) of mRNAs and affect the translation and/or stability of that mRNA, leading to a reduction in protein levels
Transfection of miR-26b duplex decreased the aggressive feature of glioma cells, suggesting that miR-26b plays a critical role in glioma development, and it may act as an anti-tumor factor in glioma cells
Our studies indicate that erythropoietin-producing hepatocellular carcinoma-A2 (EphA2) is a novel target gene of miR26b, and the direct interaction between miR-26b and EphA2 mRNA is supported by several lines of evidence: (1) the 39UTR of both human and murine EphA2 mRNAs contain a putative binding site for miR-26b with significant seed match; (2) miR-26b suppresses the activity of a luciferase reporter fused with the 39UTR of EphA2 mRNA in an miRNA response elements (MREs) dependent manner; (3) miR-26b represses the endogenous expression of human/ murine EphA2 at both the mRNA and protein level; (4) A previous study has shown that EphA2 gene knockdown by small interference RNA (siRNA) resulted in failure of Vasculogenic mimicry (VM) formation [29]
Summary
MicroRNAs (miRNAs) are short single stranded RNA molecules, which serve as master regulators of gene expression. miRNAs regulate gene expression in a sequence-specific fashion; miRNAs bind to 39untranslated regions (UTRs) of mRNAs and affect the translation and/or stability of that mRNA, leading to a reduction in protein levels. MicroRNAs (miRNAs) are short single stranded RNA molecules, which serve as master regulators of gene expression. The miR-17miR-92 cluster in T-cell acute lymphoblastic leukemia reduces the level of the transcription factor E2F1 [5,6]; miR-21 downregulates the tumor-inhibiting factor PTEN in lung cancer cells; and miR-125b is an important repressor of p53 and inhibits p53induced apoptosis in human neuroblastoma cells [7]. The let-7 family represses Ras and Myc oncogenes in cancers [8,9], and the miR-15-miR-16-1 cluster down-regulates Bcl-2 and induces apoptosis in a leukemic cell line model [10]. MicroRNAs (miRNAs) are short, non-coding RNAs that regulate the expression of multiple target genes. Its underlying mechanism of action has not been determined
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