Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Meningiomas, one of the largest subgroup of intracranial tumours are generally benign, but can progress to malignancy. They are classified into the three World Health Organization grades: benign, atypical and anaplastic meningiomas. Various histopathological features have been associated with aggressiveness or recurrence. Several genes have been suggested as prognostic factors, but molecular signatures have not permitted the classification of the tumours into the three grades. We have performed a microarray transcriptomic study on 17 meningiomas of different malignancy using CodeLink Uniset Human Whole Genome Bioarrays to try to distinguish the different grades and histopathological subtypes. Unsupervised hierarchical clustering classified the meningiomas into groups A, B and C, which corresponded to the three grades except for 3 benign meningiomas with higher proliferation indexes and/or recurrence, included in the atypical group. Several genes involved in cell adhesion (CD44, LOX), cell division (CKS2, BIRC5 and UBE2C), cell differentiation (Notch1) or signal transduction (ARHGAP28) were upregulated, whereas tumour suppressor genes (LR1B, DRR1, PLZF, GPX3, SYNPO, TIMP3 and HOPS) and genes involved in cell adhesion (PROS1), proliferation (SERPINF1 and PDGFD) and differentiation (AOX1) were downregulated in groups B and C compared to group A. In the benign tumours, we identified genes with signatures specific for fibroblastic meningiomas (FBLN1, Tenascin C and MMP2 encoding extracellular matrix proteins) and for meningothelial meningiomas (MLPH, DEFB1 and FAT3), suggesting different mechanisms involved in the tumorigenesis of these subtypes. This microarray-based expression profiling study revealed candidate genes and pathways that may contribute to a better understanding of the recurrence of a benign meningioma. Our results might make it possible to determine which benign meningiomas might recur despite complete resection, and will provide helpful information for neurosurgeons in the follow-up of the patients.
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PMID:Microarray gene expression profiling in meningiomas: differential expression according to grade or histopathological subtype. 1988 62

Neuroblastoma is one of the most common paediatric cancers, described as unpredictable due to diverse patterns of behaviour. WWOX is a tumour suppressor gene whose expression is reduced in many tumour types. Loss of its expression was shown to correlate with more aggressive disease stage and mortality rate. The aim of this study was to investigate the role of the WWOX tumour suppressor gene in neuroblastoma formation. We performed real-time RT-PCR to analyse levels of WWOX expression in 22 neuroblastic tumour samples in correlation with genes involved in cell cycle regulation (CCNE1, CCND1), proliferation (MKI67), apoptosis (BCL2, BIRC5, BAX) and signal transduction (EGFR, ERBB4). We also evaluated two potential mechanisms - promoter methylation (MethylScreen method) and loss of heterozygosity (LOH) status, which could be connected with regulation of WWOX gene expression. We found a positive correlation between WWOX gene and BCL2 and HER4 JM-a and negative with cyclin D1 and E1. Our observations are consistent with previous findings and emphasise the role of WWOX in cell cycle and apoptosis regulation. Moreover, strong positive association with HER4 JM-a in this tumour type may indicate a role for WWOX in neuroblastoma cell differentiation. The presented results indicate that LOH in locus D16S3096 (located in intron 8) may be involved in the regulation of WWOX mRNAexpression. However, no association between methylation status of WWOX promoter and its expression was observed.
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PMID:The correlation analysis of WWOX expression and cancer related genes in neuroblastoma- a real time RT-PCR study. 2445 56

miRNAs are short non-coding RNAs which function as oncogenes or tumour suppressor gene and regulate gene expression by controlling targets that play role in cancer development and progression. Numerous recent studies have established an association of abnormal expression of miRNA with cervical cancer progression. Although the number of reported deregulated miRNA in cervical cancer is increasing, only a few associations between miRNA and their targets have been studied in cervical cancer. Therefore, we performed a systematic analysis of known dysregulated miRNAs involved in cervical cancer so as to identify critical miRNA targets that could pave way for therapeutic solutions. In this study, miRNAs reported to be dysregulated in cervical cancer were collected and their targets predicted using TargetScan, PicTar and miRanda. These targets were subsequently compared with previously curated gene dataset involved in cervical cancer to derive the putative target dataset. We then compared network properties (composed of degree, betweenness centrality, closeness centrality and clustering coefficient) of the putative, validated and human protein-protein interaction network. Based on the topological properties genes were ranked and observed that the gene targets BIRC5 (survivin), HOXA1 and RARB presenting with high Novoseek score of Genecards were enriched in cervical cancer. BIRC5 is an anti- apoptotic protein while HOXA1 and RARB are transcription factors which play critical role in altering the level of cell cycle and apoptosis associated proteins. Also, miRNA-mRNA network was constructed and it was found that miR-203 and miR-30b could target these genes. The analysis indicates that the genes BIRC5, HOXA1 and RARB are critical targets that play an important regulatory role in cervical cancer pathogenesis.
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PMID:Identification of critical microRNA gene targets in cervical cancer using network properties. 2506 11

The Hippo signaling pathway plays a crucial role in regulating tissue homeostasis, organ size, tumorigenesis and cancer chemoresistance when deregulated. Physiologically, the Hippo core kinase cassette that consists of mamma-lian STE20-like protein kinase 1/2 (MST1/2), and large tumour suppressor 1/2 (LATS1/2), together with the adaptor proteins Salvador homologue 1 (SAV1) and MOB kinase activator 1 (MOB1), tightly restricts the activities of homologous oncoproteins Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) to low levels. However, how the Hippo kinase cassette core components are simultaneously inhibited, to exhibit constitutively inactivated Hippo signaling and activated YAP/TAZ in cancer remains puzzling. Herein, we reported that miR-181c directly repressed MST1, LATS2, MOB1 and SAV1 expression in human pancreatic cancer cells. Overexpression of miR-181c induced hyperactivation of the YAP/TAZ and enhanced expression of the Hippo signaling downstream genes CTGF, BIRC5 and BLC2L1, leading to pancreatic cancer cell survival and chemoresistance in vitro and in vivo. Importantly, high miR-181c levels were significantly correlated with Hippo signaling inactivation in pancreatic cancer samples, and predicted a poor patient overall survival. These findings provide a novel mechanism for Hippo signaling inactivation in cancer, indicating not only a potentially pivotal role for miR-181c in the progression of pancreatic cancer, but also may represent a new therapeutic target and prognostic marker.
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PMID:Upregulation of miR-181c contributes to chemoresistance in pancreatic cancer by inactivating the Hippo signaling pathway. 2656 Dec 4