Abstract
BackgroundRecent studies have linked chemotherapy resistance to the altered expression of microRNAs (miRNAs). Thus, miRNA-based approaches to modulating sensitivity to temozolomide (TMZ) may overcome chemoresistance. The aim of the present study was to investigate whether miR-136 could modulates glioma cell sensitivity to TMZ.MethodsThe proliferation of glioma U251 cell line was evaluated by MTT assay. The expression of astrocyte elevated gene-1 (AEG-1)was detected by real‑time polymerase chain reaction (RT-PCR)and Western blot. The luciferase reporter gene was used to test whether AEG-1 was the target of the miR-136.ResultsThe MTT assay showed that U251 cells with miR-136 overexpression were significantly more sensitive to the therapy of TMZ than control cells. Luciferase assays revealed that miR-136 directly targeted the 3’UTR of AEG-1. qRT–PCR and western blotting analysis found that AEG-1 expression at the mRNA and protein levels decreased in the miR-136 mimic-treatment group relative to control group. Downregulation of AEG-1 expression by siRNAs, U251 cells became more sensitive to the therapy of TMZ. In addition, the enhanced growth-inhibitory effect by the miR-136 mimics transfection was enhanced after the addition of AEG-1 siRNA.ConclusionsThe present study provides the first evidence that miR-136 plays a key role in TMZ resistance by targeting the AEG-1 protein in glioma cell line, suggesting that miR-136 can be used to predict a patient’s response to TMZ therapy as well as serve as a novel potential maker for glioma therapy.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_173
Highlights
Recent studies have linked chemotherapy resistance to the altered expression of microRNAs
Overexpression of miR-136 correlates with cytotoxic activity of TMZ in U251 cells In order to explore the role of miR-136 in U251 cells, transfection with plasmids, pre-miR-136 or scrambled pre-miR control, was performed
To evaluate the effect of miR-136 on the cytotoxic activity of TMZ in U251 cells, MTT assay was performed on the pre- miR-136 transfected cells, the Con and miR-Con groups combined with various concentrations of TMZ
Summary
Recent studies have linked chemotherapy resistance to the altered expression of microRNAs (miRNAs). The aim of the present study was to investigate whether miR-136 could modulates glioma cell sensitivity to TMZ. Glioma is the most common type of primary brain tumor, originating in glial cells, with poor prognosis during the past 40 years [1]. Malignant gliomas, including glioblastoma multiforme (GBM) and anaplastic astrocytomas are the most common primary brain tumors [2]. In previous decades, accumulating studies have demonstrated that miRNAs act as key regulators in the development and progression of various types of cancer, including malignant glioma [6]. MiR-136 was reported to be markedly upregulated in the Jurkat cell line and targeted tumor suppressor PTEN, suggesting a possible significance of miR-136 in cancer development and progression [8,9]. MiRNA-based approaches to modulating sensitivity to TMZ may overcome chemoresistance
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