miR-155 is up-regulated in primary and secondary glioblastoma and promotes tumour growth by inhibiting GABA receptors

Marsigliante, Santo

doi:10.3892/ijo.2012.1420

Cited by 36 publications

(22 citation statements)

References 35 publications

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“…For the other gene set, the genes most likely to influence the pathway are SNAP25 ( synaptosomal-associated protein, 25kDa ), SYT1 ( synaptotagmin I ), SLC32A1 [ solute carrier family 32 (GABA vesicular transporter), member 1 ], glutamate decarboxylase genes ( GAD2, GAD1 ), RIMS ( regulating synaptic membrane exocytosis 1 ) and STX1A [ syntaxin 1A (brain) ]. These results may be related to several studies describing down-regulation of GABA-A receptor during glioma progression (D’Urso et al ., 2012; Desrues et al ., 2012; Smits et al ., 2012). …”

Section: Predicting Genes and Pathways Associated With Mda-9 Dysresupporting

confidence: 80%

Examination of Epigenetic and other Molecular Factors Associated with mda-9/Syntenin Dysregulation in Cancer Through Integrated Analyses of Public Genomic Datasets

Bacolod

Das

Sokhi

et al. 2015

Advances in Cancer Research

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mda-9/Syntenin (melanoma differentiation-associated gene 9) is a PDZ domain-containing, cancer invasion-related protein. In this study, we employed multiple integrated bioinformatic approaches to identify the probable epigenetic factors, molecular pathways, and functionalities associated with mda-9 dysregulation during cancer progression. Analyses of publicly available genomic data (e.g., expression, copy number, methylation) from TCGA, GEO, ENCODE, and Human Protein Atlas projects led to the following observations: a) mda-9 expression correlates with both copy number and methylation level of an intronic CpG site (cg17197774) located downstream of the CpG island, b) cg17197774 methylation is a likely prognostic marker in glioma, c) Among 22 cancer types, melanoma exhibits the highest mda-9 level, and lowest level of methylation at cg17197774, d) cg17197774 hypomehtylation is also associated with histone modifications (at the mda-9 locus) indicative of more active transcription, e) Using Gene Set Enrichment Analysis (GSEA), and the VIGOR (Virtual Gene Over-expression or Repression ) analytical scheme, we were able to predict mda-9’s association with extracellular matrix organization (e.g., MMPs, collagen, integrins), IGFBP2 and NF-κB signaling pathways, phospholipid metabolism, cytokines (e.g., interleukins), CTLA-4, and components of complement cascade pathways. Indeed, previous publications have shown that many of the aforementioned genes and pathways are associated with mda-9’s functionality.

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Section: Predicting Genes and Pathways Associated With Mda-9 Dysresupporting

confidence: 80%

Examination of Epigenetic and other Molecular Factors Associated with mda-9/Syntenin Dysregulation in Cancer Through Integrated Analyses of Public Genomic Datasets

Bacolod

Das

Sokhi

et al. 2015

Advances in Cancer Research

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“…Up-regulation of microRNA miR-155 inhibits γ-aminobutyric acid A receptor 1 (GABRA1, target of methyprylon) and promotes tumor growth. 19 The targets of the fourth drug (bromfenac) are cox1 and cox2, which are well-known to be involved in inflammation, which in turn has been implicated in cancer. 20 …”

Section: Resultsmentioning

confidence: 99%

Exploring a structural protein–drug interactome for new therapeutics in lung cancer

Peng

Wang

et al. 2014

Mol. BioSyst.

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The pharmacology of drugs is often defined by more than one protein target. This property can be exploited to use approved drugs to uncover new targets and signaling pathways in cancer. Towards enabling a rational approach to uncover new targets, we expand a structural protein-ligand interactome (http://www.biodrugscreen.org) by scoring the interaction among 1,000 FDA-approved drugs docked to 2,500 pockets on protein structures of the human genome. This afforded a drug-target network whose properties compared favorably with previous networks constructed with experimental data. Among drugs with highest degree and betweenness two are cancer drugs and one is currently used for treatment of lung cancer. Comparison of predicted cancer and non-cancer targets reveals that the most cancer-specific compounds were also the most selective compounds. Analysis of compound flexibility, hydrophobicity, and size showed that the most selective compounds were low molecular weight fragment-like heterocycles. We use a previously-developed screening approach using the cancer drug erlotinib as a template to screen other approved drugs that mimic its properties. Among the top 12 ranking candidates, four are cancer drugs, two of them kinase inhibitors (like erlotinib). Cellular studies using non-small cell lung cancer (NSCLC) cells revealed that several drugs inhibited lung cancer cell proliferation. We mined patient records at the Regenstrief Medical Record System to explore possible association of exposure to three of these drugs with occurrence of lung cancer. Preliminary in vivo studies using non-small cell lung cancer (NCLSC) xenograft model showed that losartan- and astemizole-treated mice had tumors that weighed 50 (p < 0.01) and 15 (p < 0.01) percent less than vehicle. These results set the stage for further exploration of these drugs and to uncover new drugs for lung cancer.

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“…Liu et al found that miR-155 may play an important role in the transformation of normal neural stem cell toward glioma stem cells [12]. Several references also have reported that elevated expression level of miR-155 promoted the proliferation and invasion of glioblastoma cells through suppressing GABA receptors [13], FOXO3a [14], and MXI1 [15]. An oligonucleotide targeting miR-155 was shown to sensitize glioma cells to taxol-induced apoptotic death [16].…”

Section: Hbp1 Is Suppressed By Mir-155 In Glioma Cellsmentioning

confidence: 95%

miR-155 contributes to the progression of glioma by enhancing Wnt/β-catenin pathway

et al. 2015

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As the most common brain tumor, glioma is featured with poor prognosis due to its resistance to current therapeutic strategies. The elucidation of etiology is believed to facilitate the development of novel effective anti-glioma treatment modalities. As a confirmed oncogenic microRNA (miRNA) in many other types of cancers, the role of miR-155 in glioma is still unknown. This study is aimed to study the role of miR-155 in the progression of glioma. Our results revealed that miR-155 was overexpressed in the collected glioma specimen, compared with noncancerous brain tissues. The suppression of miR-155 attenuated the proliferation of glioma cells and the activation of Wnt pathway. Silencing miR-155 was also able to suppress the growth of U-87 MG glioma xenografts in mice. Pearson analysis indicated that miR-155 level was inversely correlated with the abundance of HMG-box transcription factor 1 (HBP1), a strong Wnt pathway inhibitor, in glioma samples. Further experiments confirmed that miR-155 suppressed the expression of HBP1 by targeting the putative miRNA recognition elements (MREs) within its messenger RNA (mRNA) 3' untranslated region (UTR). Furthermore, HBP1 small interfering RNA (siRNA) abolished the effect of miR-155 suppression on the proliferation of glioma and the activation of Wnt pathway. Taken together, miR-155 promoted the progression of glioma by enhancing the activation of Wnt pathway. Thus, targeting miR-155 may be an effective strategy for glioma treatment.

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miR-155 is up-regulated in primary and secondary glioblastoma and promotes tumour growth by inhibiting GABA receptors

Cited by 36 publications

References 35 publications

Examination of Epigenetic and other Molecular Factors Associated with mda-9/Syntenin Dysregulation in Cancer Through Integrated Analyses of Public Genomic Datasets

Examination of Epigenetic and other Molecular Factors Associated with mda-9/Syntenin Dysregulation in Cancer Through Integrated Analyses of Public Genomic Datasets

Exploring a structural protein–drug interactome for new therapeutics in lung cancer

miR-155 contributes to the progression of glioma by enhancing Wnt/β-catenin pathway

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