Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The inheritance of a G allele in position 61 in the 5'UTR of the epidermal growth factor (EGF) gene has been reported to increase melanoma susceptibility, a finding we have investigated in this study. The most potent phenotypic risk factor for melanoma is the atypical mole syndrome (AMS) phenotype. Our hypothesis is that the AMS is genetically determined and that nevus genes are also low penetrance melanoma susceptibility genes. We report that the G allele frequencies were the same in 697 healthy women and 380 melanoma cases (OR 0.97, 95% CI 0.8-1.2 p=0.76). We therefore found no evidence that this polymorphism is a melanoma susceptibility gene. Furthermore, we found no evidence that the polymorphism controls the nevus phenotype (nevus number, number atypical nevi or AMS phenotype). We did find some evidence that the G allele may be associated with decreased tumor Breslow thickness (OR 0.5, 95% CI 0.3-0.9) for the A/A genotype versus A/G and G/G combined in tumors of thickness >3.5 vs < or =3.5 mm and may therefore act as a predictor of survival, although this finding is not in accord with the original report. This is the second study to find no association between EGF +61 and melanoma susceptibility.
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PMID:The relationship between the epidermal growth factor (EGF) 5'UTR variant A61G and melanoma/nevus susceptibility. 1537 2

A common single nucleotide polymorphism (SNP) in the 5' untranslated region (5'UTR) of the epidermal growth factor (EGF) gene modulates the level of transcription of this gene and hence is associated with serum levels of EGF. This variant may be associated with melanoma risk, but conflicting findings have been reported. An Australian melanoma case-control sample was typed for the EGF+61A>G transversion (rs4444903). The sample comprised 753 melanoma cases from 738 families stratified by family history of melanoma and 2387 controls from 645 unselected twin families. Ancestry of the cases and controls was recorded, and the twins had undergone skin examination to assess total body nevus count, degree of freckling and pigmentation phenotype. SNP genotyping was carried out via primer extension followed by matrix-assisted laser desorption time of flight (MALDI-TOF) mass spectroscopy. The EGF+61 SNP was not found to be significantly associated with melanoma status or with development of nevi or freckles. Among melanoma cases, however, G homozygotes had thicker tumors (p=0.05), in keeping with two previous studies. The EGF polymorphism does not appear to predispose to melanoma or nevus development, but its significant association with tumor thickness implies that it may be a useful marker of prognosis.
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PMID:Epidermal growth factor gene (EGF) polymorphism and risk of melanocytic neoplasia. 1537 2

We compared microRNA profiles between choriocarcinoma and non-cancerous trophoblasts, and revealed that miR-199b was underexpressed in choriocarcinoma. By computational prediction and microarray studies, SET (protein phosphatase 2A inhibitor) was shown to be one of the target genes regulated by miR-199b. Ectopic expression of miR-199b inhibited endogenous SET protein levels and the activity of the luciferase reporter containing the 3'-UTR of SET. Further comparisons of formalin-fixed paraffin-embedded human choriocarcinoma, mole, and non-cancer trophoblast tissues confirmed the initial findings of low miR-199b expression and SET upregulation in choriocarcinomas, suggesting that microRNA-dysregulated SET protein may account for the rapid growth seen with choriocarcinomas.
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PMID:Decreased expression of microRNA-199b increases protein levels of SET (protein phosphatase 2A inhibitor) in human choriocarcinoma. 1990 Jul 56

MicroRNAs (miRNAs) regulate gene expression by repressing translation or directing sequence-specific degradation of complementary mRNA. Here, we report that expression of miR-205 is significantly suppressed in melanoma specimens when compared with nevi and is correlated inversely with melanoma progression. miRNA target databases predicted E2F1 and E2F5 as putative targets. The expression levels of E2F1 and E2F5 were correlated inversely with that of miR-205 in melanoma cell lines. miR-205 significantly suppressed the luciferase activity of reporter plasmids containing the 3'-UTR sequences complementary to either E2F1 or E2F5. Overexpression of miR-205 in melanoma cells reduced E2F1 and E2F5 protein levels. The proliferative capacity of melanoma cells was suppressed by miR-205 and mediated by E2F-regulated AKT phosphorylation. miR-205 overexpression resulted in induction of apoptosis, as evidenced by increased cleaved caspase-3, poly-(ADP-ribose) polymerase, and cytochrome c release. Stable overexpression of miR-205 suppressed melanoma cell proliferation, colony formation, and tumor cell growth in vivo and induced a senescence phenotype accompanied by elevated expression of p16INK4A and other markers for senescence. E2F1 overexpression in miR-205-expressing cells partially reversed the effects on melanoma cell growth and senescence. These results demonstrate a novel role for miR-205 as a tumor suppressor in melanoma.
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PMID:miRNA-205 suppresses melanoma cell proliferation and induces senescence via regulation of E2F1 protein. 2145 83

Therapy of melanoma patients harboring activating mutations in the BRAF (V-raf murine sarcoma viral oncogene homolog B1) oncogene with a combination of BRAF and MEK inhibitors is plagued by the development of drug resistance. Mutational events, as well as adaptive mechanisms, contribute to the development of drug resistance. In this context we uncover here the role of a miRNA, miR-579-3p. We first show that low expression of miR-579-3p is a negative prognostic factor correlating with poor survival. Expression levels of miR-579-3p decrease from nevi to stage III/IV melanoma samples and even further in cell lines resistant to BRAF/MEK inhibitors. Mechanistically, we demonstrate that miR-579-3p acts as an oncosuppressor by targeting the 3'UTR of two oncoproteins: BRAF and an E3 ubiquitin protein ligase, MDM2. Moreover miR-579-3p ectopic expression impairs the establishment of drug resistance in human melanoma cells. Finally, miR-579-3p is strongly down-regulated in matched tumor samples from patients before and after the development of resistance to targeted therapies.
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PMID:miR-579-3p controls melanoma progression and resistance to target therapy. 2750 95

Phosphatase and tensin homolog (PTEN) is a tumor-suppressor gene. PTEN pseudogene (PTENp) acts as an endogenous RNA, which regulates its parental gene by competitively binding to the 3' UTR of PTEN gene in the human. Despite the importance of this pseudogene, little is known about the molecular evolution of PTENp in mammals. In this study, we identified 37 pseudogenes from 65 mammalian genomes. Among them, 32 were from rodents or primates. Phylogenetic analyse showed a complex evolutionary history of this gene family. Some PTENps were shared both in primates and rodents. However, some PTENps were shown to be species-specific, such as the tasmanian devil PTENp1, nine banded armadillo PTENp1 and gibbon PTENp1. Most interestingly, the naked mole rat (NMR), an anticancer model organism, possessed 17 copies of PTENps, which were classified into four clades based on the phylogenetic analyses. Furthermore, we found that all the 3'UTR of PTEN and PTENps shared common microRNA (MicroRNA) binding sites in NMR, based on our prediction of specific MicroRNA binding sites. Our findings suggested that multiple gene duplications have occurred in the formation of PTEN/PTENp gene family during the evolution of mammals. Some PTENps were relatively ancient and were shared by primates and rodents; others were newly originated through species- specific gene duplications. PTENps in NMR may function as competitive endogenous RNAs (ceRNAs) to regulate their counterpart genes by competing for common MicroRNAs, which may be one of the interpretations for the cancer resistance in NMR.
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PMID:Molecular Evolution of PTEN Pseudogenes in Mammals. 2793 83

Melanoma demonstrates altered patterns of DNA methylation that are associated with genetic instability and transcriptional repression of numerous genes. Active DNA demethylation is mediated by TET enzymes that catalyze conversion of 5-methylcytosine (mC) to 5-hydroxymethylcytosine (hmC). Loss of hmC occurs in melanoma and correlates with disease progression. Here we analyzed the genomic distribution of hmC along with mC in nevus and melanoma using oxidative bisulfite chemistry combined with high-density arrays. HmC was enriched relative to mC at enhancers, 5'UTR regions and CpG shores in nevus and melanoma samples, pointing to specific TET enzyme activity. The proportion of interrogated CpG sites with high hmC levels was lower in melanoma (0.54%) than in nevus (2.0%). Depletion of hmC in melanoma was evident across all chromosomes and intragenic regions, being more pronounced in metastatic than in non-metastatic tumors. The patterns of hmC distribution in melanoma samples differed significantly from those in nevus samples, exceeding differences in mC patterns. We identified specific CpG sites and regions with significantly lower hmC levels in melanoma than in nevus that might serve as diagnostic markers. Differentially hydroxymethylated regions localized to cancer-related genes, including the PTEN gene promoter, suggesting that deregulated DNA hydroxymethylation may contribute to melanoma pathogenesis.
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PMID:Genome-wide characterization of 5-hydoxymethylcytosine in melanoma reveals major differences with nevus. 3201 78