Abstract
BackgroundmiRNA-184 is an oncogene in human hepatocellular carcinoma but acts as a tumor suppressor in tongue squamous cell carcinoma. Studies have shown that miR-184 was down-regulated in glioma and TNFα-induced protein 2 (TNFAIP2) was closely related to tumorigenesis. This study aimed to determine the functions of miR-184 in glioma and the mechanisms of miRNA-184-TNFAIP2 mediated glioma progression.MethodsReal-time reverse-transcription PCR detected expression of miR-184 and TNFAIP2. U87 and U251 cells were transfected with miR-184 mimic, inhibitor, or negative control miRNA, and their invasion abilities were assayed. Cellular proliferation was measured by the cell counting kit-8 assay. miR-184 effects on glioma cell apoptosis and cell cycle were assessed by flow cytometer. Biological information software have predicted that miR-184 could target TNFα-induced protein 2 (TNFAIP2), Which was further validated by Western blot and qRT-PCR in glioma cells. In vivo, U87 cells transduced with either lentiviral over-expressed miR-184 or control lentivirus were injected into nude mice subcutaneously and intracranial respectively.ResultsExpression of miR-184 was significantly lower in glioma tissues and cell-lines compared to normal brain tissues. Protein and mRNA expression of TNFAIP2 were inversely correlated with miR-184 in glioma. In vitro, proliferation and invasion abilities were also decreased in U87 and U251 cells after transfection with miR-184 mimic. In vivo, the xenografted tumor size in the miR-184 overexpressing group were smaller than the miR-NC group. Concordantly, U87 and U251 cells transfected with miR-184 mimic had a higher apoptosis rate, triggering an accumulation of cells at the G0/G1 phase and decreased cells in S-phase.ConclusionsmiR-184 could regulate TNFAIP2 expression and affected its translation in glioma. miR-184 could also inhibit glioma progression and might serve as a novel therapeutic target in glioma.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-015-0142-9) contains supplementary material, which is available to authorized users.
Highlights
Gliomas are the most common and lethal primary brain tumors in adults
Quantitative reverse transcriptase PCR results demonstrated that miR-184 expression in 49 glioma tissues was markedly lower than in 8 noncancerous brain tissues and decreased with the increasing degree of malignancy in gliomas
MiR-184 expression was examined in glioma cell-lines (U87, U251, U373, A72, SHG44)
Summary
Gliomas are the most common and lethal primary brain tumors in adults. Patients with newly diagnosed glioblastoma multiforme (GBM), the most malignant histological subtype of glioma, have a median survival period of approximately one year [1,2,3]. Despite comprehensive therapies including surgical resection, radiation, and MicroRNAs are endogenous small noncoding RNAs with lengths of approximately 18–25 nucleotides. They regulate gene expression at the transcriptional and posttranscriptional level by completely or incompletely. The plasma expression levels of miR-184 were associated with the presence of primary tumors and might be used as a novel cancer marker in tongue squamous cell carcinoma [14]. A study by Emdad et al confirmed that miR184 is down-regulated in human malignant glioma cells and tumor tissue as compared with their non-neoplastic counterpart [18]. This study aimed to determine the functions of miR-184 in glioma and the mechanisms of miRNA-184-TNFAIP2 mediated glioma progression
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