De-repression of CTGF via the miR-17-92 cluster upon differentiation of human glioblastoma spheroid cultures

Ernst, Aurélie; Campos, Benito; Meier, Jan; Devens, Frauke; Liesenberg, Franziska; Wolter, Marietta; Reifenberger, Guido; Herold‐Mende, Christel; Lichter, Peter; Radlwimmer, Bernhard

doi:10.1038/onc.2010.83

Cited by 137 publications

(106 citation statements)

References 57 publications

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“…[29][30][31] EGFR, MET, PDGFR, and miRNAs have been implicated in the regulation of GSC functions. [32][33][34][35][36][37][38][39][40] This study identifies for the first time miR-134 as a critical RTK-regulated tumor suppressive hub that targets KRAS and STAT5B and mediates RTK and RTK inhibitor effects on GBM malignancy.…”

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confidence: 88%

Multiple receptor tyrosine kinases converge on microRNA-134 to control KRAS, STAT5B, and glioblastoma

Zhang

Mueller

et al. 2014

Cell Death Differ

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Receptor tyrosine kinases (RTKs) are co-deregulated in a majority of glioblastoma (GBM), the most common and most deadly brain tumor. We show that the RTKs MET, EGFR, and PDGFR regulate microRNA-134 (miR-134) in GBM. We find that miR-134 is downregulated in human tumors and cancer stem cells and that its expression inversely correlates with the activation of MET, EGFR, and PDGFR. We demonstrate that miR-134 inhibits cancer cell and stem-cell proliferation, survival, and xenograft growth, as well as cancer stem-cell self-renewal and stemness. We identify KRAS and STAT5B as targets of miR-134, and establish molecular and functional links between RTKs, miR-134, KRAS/STAT5B and malignancy in vitro and in vivo. We show that miR-134 induction is required for the anti-tumor effects of RTK inhibitors. We also uncover the molecular pathways through which RTKs regulate miR-134 expression and demonstrate the involvement of MAPK signaling and the KLF4 transcription factor. We therefore identify miR-134 as a novel RTK-regulated tumor-suppressive hub that mediates RTK and RTK-inhibitor effects on GBM malignancy by controlling KRAS and STAT5B. Cell Death and Differentiation (2014) 21, 720-734; doi:10.1038/cdd.2013; published online 17 January 2014 microRNAs (miRNAs) regulate a wide variety of physiological and pathological processes. 1-3 miRNAs modulate protein expression by binding to the 3 0 untranslated region (3 0 UTR) of target mRNA and promoting RNA degradation and/or inhibiting translation. Single miRNAs can regulate multiple molecules, highlighting a powerful mechanism for the regulation of redundant and cross-talking signal transduction pathways. 4 miRNA dysregulation is a common feature of neoplasia and numerous miRNAs have been characterized as oncogenes or tumor suppressors in many cancers including in glioblastoma (GBM). 3,[5][6][7][8][9][10][11] microRNA-134 (miR-134) has been implicated in the regulation of physiological and developmental processes. It was shown to promote mouse embryonic stem-cell differentiation, dendritogenesis, and stage-specific cortical development. 12-17 miR-134 is downregulated by SIRT1 and involved in synaptic plasticity and memory formation. 18 miR-134 expression is regulated by MEF2 in dendritogenesis 14 and GBM. 19 GBM is the most common and most deadly primary malignant brain tumor. 20,21 The Cancer Genome Atlas and other studies have shown that aberrant expression or activation of the receptor tyrosine kinases (RTKs) EGFR, MET, and PDGFR occurs in a majority of GBM and correlates with poor prognosis. 22 Importantly, multiple RTKs are co-activated in the same GBM tumors and tumor cells. 23,24 KRAS, STAT3, and STAT5 are activated by RTKs and mediate their oncogenic effects. [25][26][27][28] The failure of current treatments for GBM is arguably due to the presence in the tumors of GBM stem cells (GSCs) that are resistant to radioand chemo-therapy and capable of maintaining and propagating the tumors. 29-31 EGFR, MET, PDGFR, and miRNAs have been implicated in the regulation of GSC f...

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confidence: 88%

Multiple receptor tyrosine kinases converge on microRNA-134 to control KRAS, STAT5B, and glioblastoma

Zhang

Mueller

et al. 2014

Cell Death Differ

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“…The expression of miR‐17‐92 cluster is up‐regulated in glioma tissues. MiR‐17‐92 cluster inhibition decreases cell proliferation and induces apoptosis in glioblastoma spheroids culture by up‐regulating the expression of CDKN1A (cyclin‐dependent kinase inhibitor 1A), E2F1 and PTEN 15. MiR‐17‐92 cluster is regarded as the first miRNA cluster with oncogenic potential,15 the cluster includes 6 single mature miRNAs, miR‐19 has been supposed to be the key oncogenic miRNA among the six members of miR‐17‐92 cluster.…”

Section: Introductionmentioning

confidence: 99%

“…MiR‐17‐92 cluster inhibition decreases cell proliferation and induces apoptosis in glioblastoma spheroids culture by up‐regulating the expression of CDKN1A (cyclin‐dependent kinase inhibitor 1A), E2F1 and PTEN 15. MiR‐17‐92 cluster is regarded as the first miRNA cluster with oncogenic potential,15 the cluster includes 6 single mature miRNAs, miR‐19 has been supposed to be the key oncogenic miRNA among the six members of miR‐17‐92 cluster. MiR‐19 is located on chromosome 13 in c13orf25 16 and its expression is up‐regulated in bladder cancer, breast cancer, pancreatic cancer, gastric cancer and laryngeal squamous cell carcinoma 17, 18, 19, 20, 21.…”

Section: Introductionmentioning

confidence: 99%

The emerging role of miR‐19 in glioma

Wang

Zhang

Hao

et al. 2018

J Cellular Molecular Medi

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Glioma has been regarded as the most common, highly proliferative and invasive brain tumour. Advances in research of miRNAs in glioma are toward further understanding of the pathogenesis of glioma. MiR‐19, a member of miR‐17~92 cluster, was reported to play an oncogenic role in tumourigenesis. Here we review the identified data about the effect of miR‐19 on proliferation, apoptosis, migration and invasion of glioma cells, the target genes regulated by miR‐19, and correlation of miR‐19 with the sensitivity of glioma cells to chemotherapy and radiotherapy. It is concluded that miR‐19 plays an important role in the pathogenesis of glioma and can be a potential target for gene therapy of glioma.

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“…It has been suggested that there is a link between miRNAs and well-known stem cell-regulating proteins [72]. It has also been reported that miR-17-92 plays a critical role in regulation of glioma stem cell (GSC) differentiation, apoptosis, and proliferation [73]. miR-451 expression reduced notably in cancer cells kept in low glucose conditions.…”

Section: Epigenetics In Human Gliomas With Some Detailsmentioning

confidence: 99%

Critical Molecular and Genetic Markers in Primary Brain Tumors with Their Clinical Importance

Yaylım¹,

Azam²,

Farooqı³

et al. 2016

Neurooncology - Newer Developments

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Classification of primary brain tumors is based mainly on histopathological characteristics. Due to the peculiarity of the central nervous system (CNS), the location of the tumor is also used in the naming of the CNS tumors. These features, histopathology, and location determine the main prognostic factors in these tumors. Updated molecular and genetic findings in the last two decades accumulated vast amount of knowledge about the biological behavior, response to the treatment, and consequently the prognosis of CNS tumors. After the clinical use of these data, a recent classification is proposed by the International Society of Neuropathology named as "integrated diagnosis."This classification considers the histopathological classification, World Health Organization (WHO) grade along with the molecular information. The emerging molecular-genetic data about the CNS tumors will allow the translational researchers to deliberately understand the oncogenic mechanisms involved in the evolution of these tumors and judge the optional treatment strategies.Evaluating the check points of cell cycle and apoptosis provides valuable information about the tumor biology (tumorigenesis). These mechanisms (pathways) also play an exclusive role in CNS tumors. Knowledge concerning the gene repressors and gene activators or some epigenetic changes in proliferative and antiproliferative pathways that regarded gliomas may yield new individualized treatment options.In this chapter, we will review the basic and translational research molecular-genetic data of gliomas with special interest on proliferative and antiproliferative pathways. Further emerging treatment options and treatment responses in gliomas will be © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.critically evaluated with regard to their histopathology, anatomical location, and molecular-genetic fingerprints.

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De-repression of CTGF via the miR-17-92 cluster upon differentiation of human glioblastoma spheroid cultures

Cited by 137 publications

References 57 publications

Multiple receptor tyrosine kinases converge on microRNA-134 to control KRAS, STAT5B, and glioblastoma

Multiple receptor tyrosine kinases converge on microRNA-134 to control KRAS, STAT5B, and glioblastoma

The emerging role of miR‐19 in glioma

Critical Molecular and Genetic Markers in Primary Brain Tumors with Their Clinical Importance

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