2017Molecular Medicine ReportsOpen access

MicroRNA‑376a inhibits cell proliferation and invasion in glioblastoma multiforme by directly targeting specificity protein 1

Yuefeng Li, Yunxia Wu, Zhigang Sun, Ruiyu Wang, Deliang Ma

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Abstract

Glioblastoma multiforme (GBM), a World Health Organization grade IV glioma, is the most common and aggressive primary brain tumor in humans. microRNAs (miRNAs) are aberrantly expressed in numerous cancer types, including GBM. Abnormally expressed miRNAs are commonly associated with malignant characteristics of GBM, including malignant growth, proliferation, apoptosis, invasion, metastasis and resistance to chemotherapy. miRNA (miR)‑376a is abnormally expressed in multiple human cancers; however, the expression pattern and role of miR‑376a in GBM, and the underlying molecular mechanisms by which miR‑376a exerts its functions remain to be elucidated. Therefore, the aim of this study was to measure miR‑376a expression and determine its biological roles in GBM as well as its associated molecular mechanism. In the present study, miR‑376a expression was markedly downregulated in GBM tissues and cell lines. Overexpression of miR‑376a markedly decreased the proliferation and invasion of GBM cells in vitro. In the present study, specificity protein 1 (SP1) was demonstrated to be a direct target of miR‑376a. In addition, a negative association between SP1 mRNA and miR‑376a expression was observed in GBM tissues. SP1 upregulation reduced the effects of miR‑376a overexpression on GBM cell proliferation and invasion. miR‑376a may be a therapeutic target for the treatment of patients with GBM.

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What this paper is about

Glioblastoma multiforme (GBM), a World Health Organization grade IV glioma, is the most common and aggressive primary brain tumor in humans. microRNAs (miRNAs) are aberrantly expressed in numerous cancer types, including GBM. Abnormally expressed miRNAs are commonly associated with malignant characteristics of GBM, including malignant growth, proliferation, apoptosis, invasion, metastasis and resistance to chemotherapy. miRNA (miR)‑376a is abnormally expressed in multiple human cancers; however, the expression pattern and role of miR‑376a in GBM, and the underlying molecular mechanisms by which miR‑376a exerts its functions remain to be elucidated. Therefore, the aim of this study was to measure miR‑376a expression and determine its biological roles in GBM as well as its associated molecular mechanism. In the present study, miR‑376a expression was markedly downregulated in GBM tissues and cell lines. Overexpression of miR‑376a markedly decreased the proliferation and invasion of GBM cells in vitro. In the present study, specificity protein 1 (SP1) was demonstrated to be a direct target of miR‑376a. In addition, a negative association between SP1 mRNA and miR‑376a expression was observed in GBM tissues. SP1 upregulation reduced the effects of miR‑376a overexpression on GBM cell proliferation and invasion. miR‑376a may be a therapeutic target for the treatment of patients with GBM.

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Available abstract

Glioblastoma multiforme (GBM), a World Health Organization grade IV glioma, is the most common and aggressive primary brain tumor in humans. microRNAs (miRNAs) are aberrantly expressed in numerous cancer types, including GBM. Abnormally expressed miRNAs are commonly associated with malignant characteristics of GBM, including malignant growth, proliferation, apoptosis, invasion, metastasis and resistance to chemotherapy. miRNA (miR)‑376a is abnormally expressed in multiple human cancers; however, the expression pattern and role of miR‑376a in GBM, and the underlying molecular mechanisms by which miR‑376a exerts its functions remain to be elucidated. Therefore, the aim of this study was to measure miR‑376a expression and determine its biological roles in GBM as well as its associated molecular mechanism. In the present study, miR‑376a expression was markedly downregulated in GBM tissues and cell lines. Overexpression of miR‑376a markedly decreased the proliferation and invasion of GBM cells in vitro. In the present study, specificity protein 1 (SP1) was demonstrated to be a direct target of miR‑376a. In addition, a negative association between SP1 mRNA and miR‑376a expression was observed in GBM tissues. SP1 upregulation reduced the effects of miR‑376a overexpression on GBM cell proliferation and invasion. miR‑376a may be a therapeutic target for the treatment of patients with GBM.

Key concepts: Oncogene, microRNA, Downregulation and upregulation, Cancer research, Cell growth, Cell cycle, Glioma, Biology

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