16S rRNA Gene Phylogenesis of Culturable Predominant Bacteria from Diseased Apostichopus japonicus(Holothuroidea,Echinodermata)

Cultured Apostichopus japonicus in China suffers from a kind of skin ulceration disease that has caused severe economic loss in recent years. The disease,pathogens of which are supposed to be bacteria by most researchers,is highly infectious and can often cause all individuals in the same culture pool to die in a very short time. The 16S rRNA gene phylogenesis of the culturable bacteria from the lesions of diseased individuals was conducted to study the biodiversity of the bacterial communities in the lesions and to identify probable pathogen(s) associated with this kind of disease. S. japonica samples were selected from a hatchery located in the eastern part of Qingdao,China. Bacterial universal primers GM5F and DS907R were used to amplify the 16S rRNA gene of bacteria colonies,and touchdown PCR was performed to amplify the target sequences. The results suggest that γ-proteobacteria(Alteromonadales and Vibrionales) of CFB group,many strains of which have been also determined as pathogens in other marine species,are the predominant bacterial genera of the diseased Apostichopus japonicus individuals.

Implication of HPV16 Infection and P21 Gene Mutation in the Carcinogenesis and Prognosis of Gastric Cancer

Objective： To investigate whether there is a synergistic carcinogenesis between the infection of human papilloma virus （HPV） and the P21 gene mutation in gastric cancer tissue and their relationship with prognosis of the patients with gastric cancer. Methods： By using PCR technique, HPV16 infection in 46 gastric cancer tissue samples was measured and by using immunohistochemical S-P method, the P21 gene mutation in gastric cancer was detected. All patients were regularly followed up for 3 years by writing letter or clinics, to detect the infection of HPV16 by PCR and the p21 gene mutation by immunohistochemical method in 46 gastric cancer tissue specimens. Results： The positive rate of HPV16 was 41.3% and the gene mutation rate of p21 was 52.17% respectively. The recurrence or remote metastasis was observed in 21 of 46 patients. The recurrence rate was 73.68% in the patients positive for HPV16 and 66.6% in those positive for p21 gene mutation. In 8 cases positive for both HPV16 and P21, 6 had recurrence or remote metastasis. Conclusion： The HPV16 infection may be one factor causing gastric cancer and it has a synergistic carcinogenesis with the p21gene mutation. The latter may be one of the prognostic indices in gastric cancer.

EXPRESSION OF P16 AND CYCLIN D1 IN THE COURSE OFCARCINOGENESIS OF THE STOMACH

Objective: To determine p16 and cyclin D1 expression in the specimen of gastric carcinoma, atypic hyperplasia, atrophic gastritis, superficial gastritis and normal gastric mucosa. Methods: Using immunohistochemical method (ABC), the samples of 58 adenocarcinomas, 22 atypic hyperplasias, 28 atrophic gastritis, 27 superficial gastritis and 15 gastric epitheliums were analyzed. Results: Positive immunostaining rate for p16 protein was the highest in normal gastric mucosa and decreased with the lesions progressing from superficial gastritis to atrophic gastritis to atypital hyperplasia and to adenocarcinoma (85%, 78.6%, 31.8%, 48.3% respectively); Positive immunostaining of cyclin D1 can observed in atrophic gastritis. With the lesions progressing from atrophic gastritis to atypical hyperplasia to adenocarcinoma, its expression rate increased (17.9%, 36.4%, 53.4% respectively), and there was a significant difference between adenocarcinoma and atrophic gastritis group (P<0.05). An interesting observation was that inverse expression between p16 and cyclin D1, was shown in most of gastric cancer detected. Conclusion: It is indicated that p16 and cyclin D1 play an important role in the gastric carcinogenesis, the inverse expression between p16 and cyclin D1 suggested that there is a suppression trend in them.

Genes Expressing Differences in Upland Cotton Fiber Development Between 12 DPA and 16 DPA

Cotton is the major dominant natural fiber crop on the earth.Although some current cotton genetics and breeding programs had made great progresses in cotton lint yield increases and disease resistance(tolerance),fiber quality has little improvement.Global understanding genes expression

The correlation of p16 and MMPs expression in cervical secretions with the angiogenesis and cell proliferation in cervical cancer tissue

Objective:To study the correlation of p16 and MMPs expression in cervical secretions with the angiogenesis and cell proliferation in cervical cancer tissue.Methods:A total of 78 patients with cervical cancer who were treated in our hospital between August 2013 and May 2016 were collected as the observation group, and patients with cervicitis who received examination in our hospital during the same period were selected as the control group. The cervical secretions were collected to determine p16, MMP-2, MMP-7 and MMP-9 levels with enzyme-linked immunosorbent assay (ELISA) kit, cervical lesion tissue samples were collected to determine angiogenesis index levels by RIA method, and ELISA kits were used to determine proliferation genes B7-H4, GBP1, Sp2, EZH2 and PKC protein expression. Pearson test was used to analyze the correlation of p16 and MMPs expression in cervical secretions with the angiogenesis and cell proliferation in cervical cancer tissue of patients with cervical cancer.Results: p16, MMP-2, MMP-7 and MMP-9 levels in cervical secretions of observation group were higher than those of control group, and COX-2, VEGFA, VEGFC, B7-H4, Sp2, EZH2 and PKC expression in cervical biopsy tissue were higher than those of control group while GBP1 expression was lower than that of control group.Conclusion:p16 and MMPs expression in cervical secretions of patients with cervical cancer can quantifiably reflect the degree of angiogenesis and proliferation of cervical cancer cells.

Association of low p16INK4a and p15INK4b mRNAs expression with their CpG islands methylation with human hepatocellular carcinogenesis

AIM:To study the significance of p16 and p15 transcription suppression with hypermethylation of their genes′5′CpG islands during human hepatocellular carcinogenesis.METHODS:The mRNA expression levels of p16 and p15 genes were evaluated in cancerous,para-cancerous and non-cancerous tissues of 20 HCC,3 normal liver tissues from 3 accidentally died healthy adults using simi-quantitatively Northerm blot.The methylation status was also assessed with methylation specfic PCR.RESULTS:p16 mRNA expression level was decressed in the cancerous tissues in 60%(12/20) of HCC patients,of which 2 cases had no p16 mRNA detected,5 cases(25%) displayed variation in the order of cancerous<para-cancerous<non-cancerous liver tissues.p15 mRNA expression level was decreased in the cancerous tissues in 50%(10/20) HCC patients,of which one case had no p15 mRNA detected,4 cases (20%) displayed variation in the order of cancerous<para-cancerous<non-cancerous liver tissues.In cancerous,para-cancerous and non-cancerous tissues,p16 promoter CpG islands hypernethylation occurred 65% ,60% and 35%,while p15 promoter CpG islands hypermethylation occurred 50%,40% and 25%.of 12 HCCs with lower p16 promoter CpG islands methylation(91.6%).Hundred percent(10/10) HCCs with lower p15 mRNA expression level showed p15 promoter CpG islands methylation.Significant correlation between 5′CpG islands methylation and p16/p15 mRNA expression suppression was found.The dexreased expression of p16/p15 mRNA or metyylation of p16.p15 promoters 5′CpG island was significantly,0.01.2,0.00271,0.0218,respectively,(p<0.05).CONCLUSION:p16 and p15 genes transcriptional inactivation might play an important role in hepataocarcinogenesis.5′CpG islands methylation might bi the major mechanism of p16 and p15 genes inactivation in primary HCC in the studied population.5′CpG islands methylation of p16 and p15 genes might be an early event in hepatocarcinogenesis.

Comethylation of p16 and MGMT genes in colorectal carcinoma:Correlation with clinicopathological features and prognostic value

AIM: To investigate the significance of p16 and O6- methylguanine-DNA methyltransferase (MGMT) genes promoter hypermethylation and K-ras mutations on colorectal tumorigenesis and progression. METHODS: p16 and MGMT methylation status was examined on 47 tumor samples, and K-ras mutational status was examined on 85 tumor samples. For methylation analysis, a methylation specific PCR (MS-PCR) method was used. RESULTS: p16 and MGMT promoter methylation was found in 51% (24/47) and 43% (20/47) of CRCs, respectively, and the K-ras mutation was found in 44% (37/85) of CRCs. Comethylation of p16 and MGMT genes was significantly associated with lower aggressiveness of the disease within a two-year period of observation. Only 27% of patients with simultaneous p 16 and MGMT methylation showed the detectible occurrence of metastasis and/or death, compared to 67% of patients without double methylation or with no methylation (3/11 vs 22/33, P < 0.05, χ2-test). In addition, p16 and MGMT comethylation showed a trend toward an association with longer survival in patients with CRCs (35.5 ± 6.0 mo vs 23.1 ± 3.2 mo, P = 0.072, Log-rank test). Progression of the disease within a two-year period was observed in 66% of patients carrying the K-ras mutation, compared to only 19% of patients with wild type K-ras (29/44 vs 7/37, P < 0.001, χ2-test). The presence of the K-ras mutation significantly correlated to shortened overall survival (20.0 ± 1.9 mo vs 37.0 ± 1.8 mo, P < 0.001, Log-rank test). The comethylation of p16 and MGMT genes was significantly associated with lower aggressiveness of the disease even when K-ras mutations were included in the analysis as an independent variable. CONCLUSION: Our data suggest that comethylation of promoters of p 16 and MGMT genes could have a prognostic value in patients with CRC. Specifically, concurrent methylation of both genes correlates with better prognosis.

CSN6 promotes tumorigenesis of gastric cancer by ubiquitin-independent proteasomal degradation of p16INK4a

Objective: CSN6 is a vital subunit of the constitutive photomorphogenesis 9(COP9) signalosome(CSN), which is responsible for development disorders and promotes ubiquitin-26 S proteasome-dependent degradation in vitro and vivo.Its role in the tumor development of gastric cancer remains unclear.In this study, we investigated the role of CSN6 in gastric cancer progression.Methods: Human gastric cancer samples were collected and immunohistochemistry was performed to identify the role of CSN6 in gastric cancer.The cell proliferation was measured by CCK-8 and the EdU incorporation method.Immunofluorescence localization and a co-immunoprecipitation study were used to show the interaction between the protein CSN6 and p16.Ubiquitination assay was performed to validate whether ubiquitination is involved in CSN6-mediated p16 degradation.BALB/c nude mice were used to produce a tumor model in order to test the effect of CSN6 on cancer growth in vivo.Results: CSN6 expression was dramatically increased in gastric cancer tissues compared with paired adjacent non-tumor tissues and CSN6 was correlated with worse overall and disease-specific survival.Additionally, we also found that CSN6 downregulated p16 protein expression, thereby promoting gastric cancer cell growth and proliferation.Moreover, CSN6 interacted with p16 and a proteasome activator REGγ(PA28γ), thereby facilitating ubiquitin-independent degradation of p16.Conclusions: CSN6 promoted the loss of p16-mediated tumor progression and played an important role in regulating ubiquitin-independent proteasomal degradation of p16.

Coordinated transcription of ANRIL and P16 genes is silenced by P16 DNA methylation

Objective： To investigate the relationship between the transcription of ANRIL, P15, P14 and P16 at the same locus and the regulation mechanism of ANRIL.Methods： Publicly available database of Cancer Cell Line Encyclopedia（CCLE） was used in bioinformatic analyses. Methylation of Cp G islands was detected by denaturing high performance liquid chromatography（DHPLC）. Gene transcript levels were determined using quantitative real-time polymerase chain reaction（q RTPCR） assays. An engineered P16-specific transcription factor and DNA methyltransferase were used to induce P16-specific DNA demethylation and methylation.Results： The expression level of ANRIL was positively and significantly correlated with that of P16 but not with that of P15 in the CCLE database. This was confirmed in human cell lines and patient colon tissue samples. In addition, ANRIL was significantly upregulated in colon cancer tissues. Transcription of ANRIL and P16 was observed only in cell lines in which the P16 alleles were unmethylated and not in cell lines with fully methylated P16 alleles.Notably, P16-specific methylation significantly decreased transcription of P16 and ANRIL in BGC823 and GES1 cells. In contrast, P16-specific demethylation re-activated transcription of ANRIL and P16 in H1299 cells（P〈0.001）.Alteration of ANRIL expression was not induced by P16 expression changes.Conclusions： ANRIL and P16 are coordinately transcribed in human cells and regulated by the methylation status of the P16 Cp G islands around the transcription start site.

Changes of p53 and Waf1p21 and cell proliferation in esophageal carcinogenesis

AIM To study the correlationship between the changes of p53, Waf1p21 and the cell proliferation determined by PCNA at different stages of human esophageal carcinogenesis. METHODS Biopsied and resected esophageal tissues from a high risk population for esophageal cancer in northern China were used in this study. All the specimens were fixed with 85% alcohol and further processed with routine histology. The avidin biotin peroxidase complex (ABC) method was used for the detection of p53, Waf1p21 and PCNA. RESULTS The strong nuclear staining for p53, Waf1p21 and PCNA was observed in the normal esophageal epithelium and the epithelia with different severities of lesions. As the lesions progressed to dysplasia (DYS) and to esophageal squamons cell carcinoma (SCC), the percentage of Waf1p21 immunoreactivity decreased. The number of Waf1p21 immunostaining positive cells increased slightly from normal to basal cell hyperplasia (BCH), but there was no further increase in DYS and in SCC. The total number of positive cells for Waf1p21 stain appeared to be lower than that of p53 in normal and BCH esophageal epithelia and much lower in DYS and SCC. The Waf1p21 positive immunostaining cells were located at the third and forth cell layers in half of the samples examined, which was 2～4 cell layers higher than that of PCNA and p53 in the same histological categories of normal, BCH and DYS. CLNCLUSION The low levels of Waf1p21 at the stage of DYS may be related to a functional loss of p53. Other mechanisms may also be responsible to the lack of Waf1p21 expression in DYS and SCC.

METHYLATION OF p16 AND p15 GENES IN MULTIPLE MYELOMA

Objective.To investigate the frequency of p16a nd p15gene methylation in multiple myeloma (MM),and its relationship with bone marrow ce ll apoptosis and clinical outcome.Methods.Twenty-two patients with MM were stu died to detect p16and p15gene methylation.Methyla-tion-specific polymerase chain rea ction(MSP)was used to detect gene methylation,and terminal trans-ferase-mediated dUTP nick end-labeling(TUNEL)was used to detect cell apoptosis.Results.p16and /or p15gene methylatoin was d etected in 10of 22patients(45.4%).There were 3pa-tients with p16gene methylation,9p atients with p15gene methylation,a nd 2patients with both genes methyla-tion.The incidence of methylation o f p15gene was higher than that of p16g ene(P<0.05).The patients with p16and /or p15gene methylation had a delayed cell apoptosis,poor respon se to chemotherapy,and a short over-all survival(OS).Conclusion.The methylation of p16and /or p15gen e plays a key role in MM apoptosis path ogenesis.The patients with both p16and p15gene me thylation had a poor prognosis.

CO-DELETION OF BOTH p15/p16 GENES CORRELATES WITH POOR PROGNOSIS NON-SMALL CELL LUNG CNACER

Objective: To investigate the relationship between co-deletion of p15/p16 genes and the prognostic significance in patients with non-small cell lung cancer (NSCLC). Methods: By using polymerase chain reaction (PCR), the loss of p15/p16 genes was examined in DNA samples from 140 NSCLC patients. Results: The rate of co-deletion in adenocarcinoma was significantly higher than that in squamous cell carcinoma (P<0.05), while it was not related to sex, age and TNM stages (P>0.05). By a five years’ follow-up survey, the survival rate of NSCLC patients with co-deletion of p15/p16 genes was obviously lower than that of patients without co-deletion (P<0.01). In the multivariate analysis, co-deletion of p15/p16 genes and TNM stages were identified as independent predictors for overall survival (P<0.01). Conclusion: Since the co-deletion of p15/p16 genes is significantly related to the prognosis of NSCLC patients, detecting co-deletion of both genes might be used as a potential marker for NSCLC prognosis.

Genes for RNA-binding proteins involved in neuralspecific functions and diseases are downregulated in Rubinstein-Taybi iNeurons

Taking advantage of the fast-growing knowledge of RNA-binding proteins(RBPs)we review the signature of downregulated genes for RBPs in the transcriptome of induced pluripotent stem cell neurons(iNeurons)modelling the neurodevelopmental Rubinstein Taybi Syndrome(RSTS)caused by mutations in the genes encoding CBP/p300 acetyltransferases.We discuss top and functionally connected downregulated genes sorted to“RNA processing”and“Ribonucleoprotein complex biogenesis”Gene Ontology clusters.The first set of downregulated RBPs includes members of hnRNHP(A1,A2B1,D,G,H2-H1,MAGOHB,PAPBC),core subunits of U small nuclear ribonucleoproteins and Serine-Arginine splicing regulators families,acting in precursor messenger RNA alternative splicing and processing.Consistent with literature findings on reduced transcript levels of serine/arginine repetitive matrix 4(SRRM4)protein,the main regulator of the neural-specific microexons splicing program upon depletion of Ep300 and Crebbp in mouse neurons,RSTS iNeurons show downregulated genes for proteins impacting this network.We link downregulated genes to neurological disorders including the new HNRNPH1-related intellectual disability syndrome with clinical overlap to RSTS.The set of downregulated genes for Ribosome biogenesis includes several components of ribosomal subunits and nucleolar proteins,such NOP58 and fibrillarin that form complexes with snoRNAs with a central role in guiding post-transcriptional modifications needed for rRNA maturation.These nucleolar proteins are“dual”players as fibrillarin is also required for epigenetic regulation of ribosomal genes and conversely NOP58-associated snoRNA levels are under the control of NOP58 interactor BMAL1,a transcriptional regulator of the circadian rhythm.Additional downregulated genes for“dual specificity”RBPs such as RUVBL1 and METTL1 highlight the links between chromatin and the RBP-ome and the contribution of perturbations in their cross-talk to RSTS.We underline the hub position of CBP/p300 in chromatin regulation,the impact of its defect on neurons’post-transcriptional regulation of gene expression and the potential use of epidrugs in therapeutics of RBP-caused neurodevelopmental disorders.

Study on the Function of ORF Genes of Porcine Circovirus-like Virus P1

[Objectives]This study was conducted to determine the functions of eight ORF genes of porcine circovirus-like virus P1.[Methods]The double-copy tandem molecular cloning of porcine circovirus-like virus P1 genome was used to construct molecular clones with eight ORFs deleted by DNA site-directed mutagenesis technology.After transfected into PK15 cells for a certain period of time,RNA were extracted and was used to verify whether the eight ORFs were deleted or not and used for gene microarry analysis.The GO functions and KEGG pathway enrichment of differentially expressed genes were analyzed.[Results]P1 ORF1 is mainly involved in the biological processes of defense response to virus,signal transduction,regulation of Rab GTPase activity,and lipid metabolic process,and involved in the molecular functions of protein phosphatase inhibitor activity,phosphatidylinositol phospholipase C activity,2 iron,2 sulfur cluster binding,phosphoric diester hydrolase activity,and Rab GTPase activator activity,and in the KEGG pathways of secretion of digestive gland and nervous system development.P1 ORF2 is mainly involved in the biological processes of positive regulation of leukocyte chemotaxis,positive regulation of cell proliferation,positive regulation of cell migration,defense response to virus,regulation of cell growth,and involved in the molecular functions of insulin-like growth factor binding,and chemokine activity,and in the KEGG pathways of cytosolic DNA-sensing pathway,RIG-I-like receptor signaling pathway,toll-like receptor signaling pathway,chemokine signaling pathway,and cytokines,cytokine-cytokine receptor interaction.The biological processes,molecular functions and related pathways involving P1 ORF3 and ORF5 are basically similar to those of ORF2.P1 ORF8 is mainly involved in the biological processes of purine ribonucleotide biosynthetic process,amino acid transport,defense response to virus,amino acid transmembrane transport,and involved in molecular functions of N6-(1,2-dicarboxyethyl)AMP AMP-lyase(fumarate-forming)activity,iron-sulfur cluster binding,amino acid transmembrane transporter activity.[Conclusions]The analysis of the ORF functions of P1 virus lays a foundation for the study of its pathogenicity and pathogenesis.

Effects of endotoxin on expression of ras, p53 and bcl-2 oncoprotein in hepatocarcinogenesis induced by thioacetamide in rats

AIM To evaluate the relationship between expression of ras, p53, bcl 2 gene products, and hepatocarcinogenesis since endotoxemia produced from lipopolysaccharide admi nistration and/or the hypophagocytic state of splenectomy significantly accelerated hepatocarcinogenesis induced by thioacetamide. 〖WTH4〗METHODS〓〖WTXFZ〗The hepatocarcinoma model was induced by oral intake of 0 03% thioacetamide for six months. During the induction of hepatocarcinoma model, rats were additionally treated with splenectomy and/or lipopolysaccharide administration. The techniques of flow cytometry, immunohistochemistry and immunoelectronmicroscopy were applied to quantitative analysis of the expression of oncogene proteins. RESULTS In this model system, overexpression of ras p21 protein mainly occurred on precancerous cell population or in early stage of hepatocyte transformation. And the levels of ras p21 declined when nuclear DNA aneuploid increased. Expression of bcl 2 protein slowly and steadily rose with more hepatocytes staying in S+G2M phases as the hepatocarcinoma became more malignant. P53 was moderately expressed during the hepatocarcinogenesis. There was no statistical correlation between endotoxemia levels and the changes of ras, p53 and bcl 2 gene products. CONCLUSION Over expression of oncogene ras p21 was likely to be a precursor of the premalignant hepatocytes and it might be responsible for the initiation of hepatocarcinogenesis. Bcl 2 protein expression is proportional to the severity of the malignancies. P53 may be a key pathway on the transformation and development of hepatocarcinoma. This study confirmed the hypothesis that there are multiple genes and multiple steps involved in hepatocarcinogenesis. Expressions of oncogene proteins reflected the properties of the premalignant and malignant cells, but not directly related to endotoxemia statistically.[JP]

Inhibitory effects of polysaccharides isolated from Phellinus gilvus on benzo(a)pyrene-induced forestomach carcinogenesis in mice

AIM: Although polysaccharides from Phellinus mushrooms are a well-known material with anti-tumor properties, there is no information about the effect of polysaccharides from Phellinus gilvus (PG) on tumor. The modulating effect of polysaccharides isolated from PG on the benzo(a)pyrene (BaP)-induced forestomach carcinogenesis in ICR female mice was investigated in this study.METHODS: A forestomach carcinogenesis model was established in 40 ICR female mice receiving oral administration of BaP for 4 wk. The mice were randomly assigned to 4 groups (10 each). The mice in each group were treated with sterile water or PG for 4 and 8 wk (SW4,PGW4, SW8, and PGW8 groups). Eight or 12 wk after the first dose of BaP, forestomachs were removed for histopathological and RT-PCR analysis.RESULTS: In histopathological changes and RT-PCR analysis, sterile water-treated mice showed significant hyperplasia of the gastric mucosa with a significantly increased expression of mutant p53 mRNA compared to mice treated with PG for 8 wk.CONCLUSION: Polysaccharides isolated from PG may inhibit BaP-induced forestomach carcinogenesis in mice bydown-regulating mutant p53 expression.

Detecting the polymorphism sites of p53 and Fas genes of Han population in Zhejiang province

BACKGROUND： It is of significance for single nucleotide polymorphisms （SNPs）, a difference of rank, which exists widely in biology, genetics and other fields. OBJECTIVE： To detect polymorphism sites in exon-4 of p53 gene, promotor of Fas gene and intron-7 of Fas gene of healthy people in Han nationality in Zhejiang province. DESIGN： Simple random sampling. SETTING： Department of Surgery of the 118 Hospital of Chinese PLA.PARTICIPANTS： A total of 80 healthy people in Han nationality were selected from hospitals in Zhejiang province from August 2005 to January 2006. There were 43 males and 37 females aged from 3 to 78 years with the mean age of 39.5 years, and all subjects were consent. DNA which was used in genetic analysis was selected from peripheral venous blood of all subjects and maintained at -20℃.METHODS： Polymorphism sites in exon-4 of p53 gene, promotor of Fas gene and intron-7 of Fas gene were detected with directly DNA sequencing technique. MAIN OUTCOME MEASURES ： Polymorphism sites in exon-4 of p53 gene, promotor of Fas gene and intron-7 of Fas gene of healthy people in Han nationality in Zhejiang province. RESULTS： A total of 80 samples were involved in the final analysis. SNPs sites were found at the 119^th base of exon-4 of p53 gene （the 72^nd codon of p53 gene）, the 670^th base of upper start codon in promotor of Fas gene （Fas-670）, and the 995^th base of intron-7 of Fas gene, especially SNPs in the 995^th base of intron-7 pf Fas gene, i.e. C→A transversion, was a new site.CONCLUSION ： One unknown SNPs site is discovered in intron-7 of Fas gene of people in Han nationality in Zhejiang province. This study also proves that the 72^nd codon exists in p53 gene and the -670 polymorphism site exists in promotor of Fas gene.

DNA methylation and carcinogenesis in digestive neoplasms

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PDRG1 at the interface between intermediary metabolism and oncogenesis

PDRG1 is a small oncogenic protein of 133 residues. In normal human tissues, the p53 and DNA damageregulated gene 1(PDRG1) gene exhibits maximal expression in the testis and minimal levels in the liver. Increased expression has been detected in several tumor cells and in response to genotoxic stress. High-throughput studies identified the PDRG1 protein in a variety of macromolecular complexes involved in processes that are altered in cancer cells. For example, this oncogene has been found as part of the RNA polymerase Ⅱ complex, the splicing machinery and nutrient sensing machinery, although its role in these complexes remains unclear. More recently, the PDRG1 protein was found as an interaction target for the catalytic subunits of methionine adenosyltransferases. These enzymes synthesize S-adenosylmethionine, the methyl donor for, among others, epigenetic methylations that occur on the DNA and histones. In fact, downregulation of S-adenosylmethionine synthesis is the first functional effect directly ascribed to PDRG1. The existence of global DNA hypomethylation, together with increased PDRG1 expression, in many tumor cells highlights the importance of this interaction as one of the putative underlying causes for cell transformation. Here, we will review the accumulated knowledge on this oncogene, emphasizing the numerous aspects that remain to be explored.