The application of multiple miRNA response elements enables oncolytic adenoviruses to possess specificity to glioma cells

Yao, Weicheng; Guo, Guocai; Zhang, Quanqin; Fan, Limin; Wu, Ning; Bo, Yongli

doi:10.1016/j.virol.2014.04.007

Cited by 32 publications

(17 citation statements)

References 36 publications

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“…Tumor angiogenesis is vital in tumor invasion. In recent years, with the discovery of microRNAs (miRNA) and their function in in-depth investigations, it was identified that miRNA contributes to the regulation of angiogenesis in glioma formation, thus affecting the invasion ability of gliomas (14,15). Previous studies demonstrated that miR-24 was upregulated in glioblastoma tissue (16)(17)(18) and promotes cell proliferation in glioma cells via cooperative regulation of MAX interactor 1, dimerization protein (19).…”

Section: Introductionmentioning

confidence: 99%

miR‑24 regulates angiogenesis in gliomas

Dai

Huang

et al. 2018

Mol Med Report

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Gliomas are one of the most common and most aggressive types of central nervous system tumor. Angiogenesis is an important basis for the growth of solid tumors, including gliomas, which is regulated by microRNAs (miRNAs). However, the mechanism remains unclear. Recently, it was demonstrated that miR‑24 was upregulated in gliomas, so the aim of the present study is to establish whether the dysregulation of miR‑24 in glioma cells promotes microvascular proliferation of endothelial cells (ECs), and to investigate the potential mechanism. miR‑24 was overexpressed or downregulated in U251 glioma cell line cells using miR‑24 mimics or inhibitors, respectively. Subsequently, the effects of conditional medium from miR‑24 mimic‑ or inhibitor‑transfected U251 cells on cell viability, migration and angiogenesis of human umbilical vein ECs (HUVECs) were examined. The expression levels of vascular endothelial growth factor (VEGF) mRNA, basic fibroblast growth factor (bFGF) mRNA, epidermal growth factor (EGF) mRNA, transforming growth factor (TGF)‑β mRNA, matrix metalloproteinase (MMP)‑2 mRNA and MMP‑9 mRNA, and the mRNA and protein levels of VEGF and TGF‑β in miR‑24 mimic‑ or inhibitor‑transfected U251 cells were obtained by reverse transcription‑quantitative polymerase chain reaction and western blot analysis, respectively. The effects of conditional medium from miR‑24 mimic‑ or inhibitor‑transfected U251 cells on expression levels of VEGF mRNA, TGF‑β mRNA, MMP‑2 mRNA and MMP‑9 mRNA, and mRNA and protein expression levels of VEGF and TGF‑β, and intracellular AKT and β‑catenin signaling in HUVECs were also examined. The results indicated that the conditional medium from miR‑24 mimic‑transfected U251 cells exhibited significantly increased cell viability, cell migration and tube formation of HUVECs. By contrast, the conditional medium from miR‑24 inhibitor‑transfected U251 cells exhibited significantly decreased cell viability, cell migration and tube formation of HUVECs. Enforced expression of miR‑24 in U251 cells may promote the cell viability and angiogenesis of HUVECs. The mRNA expression levels of VEGF, bFGF, EGF, TGF‑β, MMP‑2 and MMP‑9 in U251 cells were significantly increased by miR‑24 mimics. Western blot detection confirmed the increased levels of VEGF and TGF‑β protein expression in U251 by miR‑24 mimics, and the decrease of VEGF and TGF‑β protein expression levels in U251 by miR‑24 inhibitors. The conditional medium from miR‑24 mimic‑transfected U251 cells increased the expression levels of the angiogenesis‑associated factors, including VEGF, TGF‑β, MMP‑2, and MMP‑9. By contrast, reduced expression of miR‑24 in U251 cells may downregulate the expression of those angiogenesis‑associated factors. Thus, miR‑24 in U251 cells may be important in the angiogenesis of HUVECs via VEGF and TGF‑β, and the intracellular signaling of AKT and β‑catenin may be involved in this process.

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Section: Introductionmentioning

confidence: 99%

miR‑24 regulates angiogenesis in gliomas

Dai

Huang

et al. 2018

Mol Med Report

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“…Since its discovery in the 1990s, miRs have research hotspots due to their functions in post-transcriptional regulation and multiple biological processes. miRs can regulate various target genes including cell growth factors, transcription factors, cell death genes and other signaling molecules, further facilitating or inhibiting cell proliferation, differentiation, apoptosis and death (21). miRs can regulate metabolism and development/growth at the post-transcriptional level (22).…”

Section: Discussionmentioning

confidence: 99%

Effects of microRNA-26b on proliferation and invasion of glioma cells and related mechanisms

Dai

Huang

et al. 2017

Molecular Medicine Reports

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Neuroglioma is the most common primary malignant tumor in neurosurgery. Due to its short survival period and high patient mortality rate, neuroglioma is a major challenge in clinics. Elucidating the pathogenic mechanisms and associated molecular targets of neuroglioma can therefore benefit diagnosis and treatment of glioma. Previous studies have established the role of microRNA (miR)‑26b in various tumors, including breast cancer, lymphoma and glioma. Its function and mechanism in neuroglioma, however, remains to be elucidated. In the present study, in vitro cultured U87 glioma cells were randomly divided into miR‑26b mimic, miR‑26b inhibitor and respective control (NC) groups. MTT assay was performed to detect the effect of miR‑26b on cell proliferation, while a cell invasion assay detected its effects on cell invasion. Caspase‑3 activity was also quantified to test cell apoptosis, followed by reverse transcription-quantitative polymerase chain reaction and western blotting to detect the variation of Bcl‑2 expression under the effect of miR‑26b. miR‑26b mimics transfection upregulated its expression in U87 cells, which had significantly reduced Bcl‑2 mRNA and protein expression levels and higher casapse3 activity, and inhibited cell proliferation and invasion compared with the control group. The transfection of miR‑26b inhibitor, in contrast, facilitated U87 cell proliferation and invasion, inhibited caspase‑3 activity and elevated Bcl‑2 mRNA/protein expression. In conclusion, miR‑26 could facilitate apoptosis and inhibit proliferation/invasion of neuroglioma cells via downregulating Bcl‑2 expression and potentiating caspase-3 activity.

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“…This enables them to guide post-transcriptional silencing of their target genes and determine the differential expression between cancerous and normal tissues (24). The negative regulation in gene expression makes it possible to utilize these miRNAs to inhibit viral replication in normal cells (25,26). Aberrant expression of miRNAs has previously been observed in numerous types of cancer (27).…”

Section: Specificity Of Ov In Succumbing Tumor Cellsmentioning

confidence: 99%

Advances in the mechanisms of action of cancer-targeting oncolytic viruses (Review)

et al. 2018

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Abstract. Cancer virotherapy mediated by oncolytic viruses (OV), has emerged as a novel and effective strategy in cancer therapeutics. Preclinical models have demonstrated anticancer activity against numerous types of cancer. Currently, a number of recombinant viruses are in late phase clinical trials, many of which have demonstrated promising results regarding the safety and reliability of the treatments, particularly when combined with standard antineoplastic therapies. In addition to molecular-targeted therapeutics, genetic engineering of the viruses allows functional complementation to chemotherapy or radiotherapy agents. Co-administration of chemotherapy or radiotherapy is imperative for an effective treatment regime. Additionally, these approaches may be used in combination with current treatments to assist in cancer management. The near future may reveal whether this renewed interest in oncological virotherapy will result in meaningful therapeutic effects in patients. The aim of the present review was to highlight how the knowledge of oncolytic viral specificity and cytotoxicity has advanced in recent years, with a view to discuss OV in clinical application and the future directions of this field.

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The application of multiple miRNA response elements enables oncolytic adenoviruses to possess specificity to glioma cells

Cited by 32 publications

References 36 publications

miR‑24 regulates angiogenesis in gliomas

miR‑24 regulates angiogenesis in gliomas

Effects of microRNA-26b on proliferation and invasion of glioma cells and related mechanisms

Advances in the mechanisms of action of cancer-targeting oncolytic viruses (Review)

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