MicroRNA‑370 suppresses the progression and proliferation of human astrocytoma and glioblastoma by negatively regulating β‑catenin and causing activation of FOXO3a

Abstract

Abstract. Certain microRNAs (miRs) regulate the progression and metastasis of various cancer types. In the present study, the role of miR-370 in the progression and proliferation of human astrocytoma and glioblastoma cells was assessed and the underlying molecular mechanism was investigated. miR-370 levels in clinical specimens of human glioma and peritumoral tissues were determined by reverse-transcription quantitative PCR. Oligonucleotide mimics and inhibitors were transfected into the U-251MG human astrocytoma cell line and the and U-87MG glioblastoma cell line and the cell viability of was determined by an MTT assay. The expression of β-catenin and forkhead box protein (FOX)O3a was determined by western blot analysis. The results revealed that the expression of miR-370 in human glioma tissues was significantly decreased compared with that in peritumoral tissues. The miR-370 levels in patients with grade III/IV gliomas were significantly decreased compared with those in grade I/II. Transfection with miR-370 mimics inhibited the proliferation of U-251MG and U-87MG cells. Furthermore, the miR-370 levels were negatively correlated with β-catenin and positively correlated with nuclear FOXO3a. In conclusion, miR-370 inhibited the proliferation of human glioma cells by regulating the levels of β-catenin and the activation of FOXO3a, suggesting that miR-370 was a tumor suppressor in the progression of human astrocytoma and glioblastoma cells. IntroductionHuman glioma is derived from the neural ectoderm and is the most common type of primary malignant tumor in human brains (1). Also in China, human gliomas are the most common type of intracranial tumor, accounting for 40-50% (2). In recent years, the risk for gliomas has been gradually increasing in young adults (3). On the World Health Organization tumor grading scale, primary gliomas are normally divided into low-grade glioma, such as fibrillary astrocytomas and pilocytic astrocytomas, and high-grade glioma, including glioblastoma and anaplastic astrocytoma (4,5).Clinical therapy of glioma depends on the size, type, grade and location of the tumor, as well as the age and overall health of the patient, and mainly consists of surgical resection followed by radiotherapy, chemotherapy, Chinese medicine treatment, gene therapy, immunotherapy and psychotherapy (6,7). However, the overall mortality rate remains high in glioma patients (8,9). It is therefore important and urgent to clarify the mechanisms of the genesis of human gliomas, which may be helpful for providing approaches for the therapy of human gliomas.MicroRNAs (miRNAs/miRs) are a class of small non-coding RNA molecules of approximately 21-25 nucleotides in length, which are conserved in plants, animals and certain types of virus (10). miRNAs are involved in the regulation of gene expression through RNA silencing and post-transcriptional gene silencing via binding to the 3'-untranslated region (3'-UTR) of specific mRNAs (11,12). miRNAs regulate diverse aspects of development and physiology, such as metabolic d...

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