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 ...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.展开更多
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), t...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.展开更多
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 di...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.展开更多
In the world,hepatocellular carcinoma(HCC)is among the top 10 most prevalent malignancies.HCC formation has indeed been linked to numerous etiological factors,including alcohol usage,hepatitis viruses and liver cirrho...In the world,hepatocellular carcinoma(HCC)is among the top 10 most prevalent malignancies.HCC formation has indeed been linked to numerous etiological factors,including alcohol usage,hepatitis viruses and liver cirrhosis.Among the most prevalent defects in a wide range of tumours,notably HCC,is the silencing of the p53 tumour suppressor gene.The control of the cell cycle and the preservation of gene function are both critically important functions of p53.In order to pinpoint the core mechanisms of HCC and find more efficient treatments,molecular research employing HCC tissues has been the main focus.Stimulated p53 triggers necessary reactions that achieve cell cycle arrest,genetic stability,DNA repair and the elimination of DNA-damaged cells’responses to biological stressors(like oncogenes or DNA damage).To the contrary hand,the oncogene protein of the murine double minute 2(MDM2)is a significant biological inhibitor of p53.MDM2 causes p53 protein degradation,which in turn adversely controls p53 function.Despite carrying wt-p53,the majority of HCCs show abnormalities in the p53-expressed apoptotic pathway.High p53 in-vivo expression might have two clinical impacts on HCC:(1)Increased levels of exogenous p53 protein cause tumour cells to undergo apoptosis by preventing cell growth through a number of biological pathways;and(2)Exogenous p53 makes HCC susceptible to various anticancer drugs.This review describes the functions and primary mechanisms of p53 in pathological mechanism,chemoresistance and therapeutic mechanisms of HCC.展开更多
BACKGROUND Dilated cardiomyopathy(DCM)is a genetically heterogeneous cardiac disorder characterized by left ventricular dilation and contractile dysfunction.The substantial genetic heterogeneity evident in patients wi...BACKGROUND Dilated cardiomyopathy(DCM)is a genetically heterogeneous cardiac disorder characterized by left ventricular dilation and contractile dysfunction.The substantial genetic heterogeneity evident in patients with DCM contributes to variable disease severity and complicates overall prognosis,which can be very poor.AIM To identify pathogenic genes in DCM through pedigree analysis.METHODS Our research team identified a patient with DCM in the clinic.Through invest-igation,we found that the family of this patient has a typical DCM pedigree.High-throughput sequencing technology,next-generation sequencing,was used to sequence the whole exomes of seven samples in the pedigree.RESULTS A novel and potentially pathogenic gene mutation-ANK2p.F3067L-was discovered.The mutation was completely consistent with the clinical information for this DCM pedigree.Sanger sequencing was used to further verify the locus of the mutation in pedigree samples.These results were consistent with those of high-throughput sequencing.CONCLUSIONS ANK2p.F3067L is considered a novel and potentially pathogenic gene mutation in DCM.展开更多
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 ...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.展开更多
[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 u...[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.展开更多
以控制R om ney Inverdale绵羊和R om ney H anna绵羊高繁殖力的骨形态发生蛋白15(BM P 15)基因为候选基因,采用PCR-RFLP方法检测BM P 15基因在高繁殖力山羊品种(济宁青山羊)以及低繁殖力山羊品种(内蒙古绒山羊、安哥拉山羊、波尔山羊)...以控制R om ney Inverdale绵羊和R om ney H anna绵羊高繁殖力的骨形态发生蛋白15(BM P 15)基因为候选基因,采用PCR-RFLP方法检测BM P 15基因在高繁殖力山羊品种(济宁青山羊)以及低繁殖力山羊品种(内蒙古绒山羊、安哥拉山羊、波尔山羊)中的多态性,同时研究该基因对济宁青山羊高繁殖力的影响。结果表明:BM P 15基因在济宁青山羊、内蒙古绒山羊、安哥拉山羊和波尔山羊中既未发生与Inverdale绵羊相同的V 31D突变,也未发生与H anna绵羊相同的Q 23T er突变。这表明BM P 15基因这2个突变位点对济宁青山羊的高繁殖力没有显著影响。展开更多
Objective:To delineate the frequency of occurrence of bla<sub>CTX-M</sub>,bla<sub>TEM</sub>,and bla<sub>SHV</sub> in Enterobacteriaceae from North-Indian tertiary hospital.Methods:A...Objective:To delineate the frequency of occurrence of bla<sub>CTX-M</sub>,bla<sub>TEM</sub>,and bla<sub>SHV</sub> in Enterobacteriaceae from North-Indian tertiary hospital.Methods:A random collection of a subset of 45 Escherichia coli(E.coli) and 28 Klebsiella pneumoniae(K.pneumoniae) that was resistant to a third generation cephalosporin and obtained during 2007-2008 was selected for detailed screening for bla<sub>CTX-M</sub>,bla<sub>TEM</sub>,and bla<sub>SHV</sub> by monoplex PCRs.The isolates demonstrating the presence of bla<sub>CTX-M</sub> alleles were characterized for the specific CTX-M-genogroup by using a multiplex PCR.Results:Resistance to cefoperazone,ceftazidime,ceftriaxone,cefotaxime, cefoxitin and piperacillin was 100%each in K.pneumoniae isolates,whereas these resistancerates for E.coli isolates were 93.1%,83.8%,91.9%,93.6%,97.3%and 97.1%,respectively. Concomitant resistance to aminoglycosides,quinolones and aztreonam was also noticed.Presence of any of the bla genes(bla<sub>CTX-M</sub>,bla<sub>TEM</sub>,and bla<sub>SHV</sub>) was noticed in a total of 28(38.4%) isolates of the 73 isolates studied.Many isolates demonstrated occurrence of these genes in various combinations.bla<sub>CTX-M</sub>,bla<sub>TEM</sub>,and bla<sub>SHV</sub> were noticed in 28.8%,10.9%and 13.7%isolates, respectively.Multiplex PCR in bla<sub>CTX-M</sub> harboring isolates demonstrated the presence of CTX-MGenogroup -1 and sequencing for the specific CTX-M-type revealed presence of CTX-M-15 type. RAPD typing showed wide diversity in isolates.Conclusions:This is amongst the premier report describing the simultaneous occurrence of blo<sub>TEM</sub>,bla<sub>SHV</sub>,and bla<sub>ampC</sub> in Indian Enterobacteriaceae and that wider dissemination of these genes,as demonstrated by diversity of isolates,raises concern and emphasizes a need for extensive search for the presence of these gene pools in Indian subcontinent.展开更多
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 p...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.展开更多
Background:Excessive abdominal fat deposition in commercial broilers presents an obstacle to profitable meat quality,feed utilization,and reproduction.Abdominal fat deposition depends on the proliferation of preadipoc...Background:Excessive abdominal fat deposition in commercial broilers presents an obstacle to profitable meat quality,feed utilization,and reproduction.Abdominal fat deposition depends on the proliferation of preadipocytes and their maturation into adipocytes,which involves a cascade of regulatory molecules.Accumulating evidence has shown that microRNAs(miRNAs)serve as post-transcriptional regulators of adipogenic differentiation in mammals.However,the miRNA-mediated molecular mechanisms underlying abdominal fat deposition in chickens are still poorly understood.This study aimed to investigate the biological functions and regulatory mechanism of miRNAs in chicken abdominal adipogenesis.Results:We established a chicken model of abdominal adipocyte differentiation and analyzed miRNA and mRNA expression in abdominal adipocytes at different stages of differentiation(0,12,48,72,and 120 h).A total of 217 differentially expressed miRNAs(DE-miRNAs)and 3520 differentially expressed genes were identified.Target prediction of DE-miRNAs and functional enrichment analysis revealed that the differentially expressed targets were significantly enriched in lipid metabolism-related signaling pathways,including the PPAR signaling and MAPK signaling pathways.A candidate miRNA,gga-miR-106-5p,exhibited decreased expression during the proliferation and differentiation of abdominal preadipocytes and was downregulated in the abdominal adipose tissues of fat chickens compared to that of lean chickens.gga-miR-106-5p was found to inhibit the proliferation and adipogenic differentiation of chicken abdominal preadipocytes.A dual-luciferase reporter assay suggested that the KLF15 gene,which encodes a transcriptional factor,is a direct target of gga-miR-106-5p.gga-miR-106-5p suppressed the posttranscriptional activity of KLF15,which is an activator of abdominal preadipocyte proliferation and differentiation,as determined with gain-and loss-of-function experiments.Conclusions:gga-miR-106-5p functions as an inhibitor of abdominal adipogenesis by targeting the KLF15 gene in chickens.These findings not only improve our understanding of the specific functions of miRNAs in avian adipogenesis but also provide potential targets for the genetic improvement of excessive abdominal fat deposition in poultry.展开更多
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 expr...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.展开更多
In the present experiment,an inhibitor of superoxide dismutase(SOD),diethyldithiocarbamate(DETC),was used to decrease SOD activity for the observation of the relation between SOD activity and carcinogenesis and the ex...In the present experiment,an inhibitor of superoxide dismutase(SOD),diethyldithiocarbamate(DETC),was used to decrease SOD activity for the observation of the relation between SOD activity and carcinogenesis and the expression of P53 protein in vivo.144 Wistar rats were used for the Present study.The results showed that the SOD activity reduction by DETC resulted markedly in the promotion of the carcinogenesis and the expression of P53 protein in the lung tissues,but the increase of SOD activity by the addition of plus SOD inhibited the pathological changes significantly.The frequency of the pathological lesions and Positive P53 expression are 36/42 and 8/42 in the animals without DETC and SOD:16/52 and 4/52 in the animals with SOD and 46/50 and 26/50 in the animals with DETC respectively.The results reported in this Paper suggest that:(1) the decrease of SOD activity enhanced the carcinogenesis induced by chemical carcinogen;(2) P53 gene may be associated with the process of tumorigenesis;and(3) at the same time the abnormal expression of P53 protein may be associated with the transition from premalignant lesions to carcinoma.展开更多
基金Supported by the National Natural Science Foundation of China.No.39670702
文摘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.
基金This work was supported by Major Medical Foundation of Shanghai (No. 9920II001).
文摘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.
文摘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.
文摘In the world,hepatocellular carcinoma(HCC)is among the top 10 most prevalent malignancies.HCC formation has indeed been linked to numerous etiological factors,including alcohol usage,hepatitis viruses and liver cirrhosis.Among the most prevalent defects in a wide range of tumours,notably HCC,is the silencing of the p53 tumour suppressor gene.The control of the cell cycle and the preservation of gene function are both critically important functions of p53.In order to pinpoint the core mechanisms of HCC and find more efficient treatments,molecular research employing HCC tissues has been the main focus.Stimulated p53 triggers necessary reactions that achieve cell cycle arrest,genetic stability,DNA repair and the elimination of DNA-damaged cells’responses to biological stressors(like oncogenes or DNA damage).To the contrary hand,the oncogene protein of the murine double minute 2(MDM2)is a significant biological inhibitor of p53.MDM2 causes p53 protein degradation,which in turn adversely controls p53 function.Despite carrying wt-p53,the majority of HCCs show abnormalities in the p53-expressed apoptotic pathway.High p53 in-vivo expression might have two clinical impacts on HCC:(1)Increased levels of exogenous p53 protein cause tumour cells to undergo apoptosis by preventing cell growth through a number of biological pathways;and(2)Exogenous p53 makes HCC susceptible to various anticancer drugs.This review describes the functions and primary mechanisms of p53 in pathological mechanism,chemoresistance and therapeutic mechanisms of HCC.
基金Supported by the Jilin Provincial Healthcare Talent Special Program,No.2019SCZT08.
文摘BACKGROUND Dilated cardiomyopathy(DCM)is a genetically heterogeneous cardiac disorder characterized by left ventricular dilation and contractile dysfunction.The substantial genetic heterogeneity evident in patients with DCM contributes to variable disease severity and complicates overall prognosis,which can be very poor.AIM To identify pathogenic genes in DCM through pedigree analysis.METHODS Our research team identified a patient with DCM in the clinic.Through invest-igation,we found that the family of this patient has a typical DCM pedigree.High-throughput sequencing technology,next-generation sequencing,was used to sequence the whole exomes of seven samples in the pedigree.RESULTS A novel and potentially pathogenic gene mutation-ANK2p.F3067L-was discovered.The mutation was completely consistent with the clinical information for this DCM pedigree.Sanger sequencing was used to further verify the locus of the mutation in pedigree samples.These results were consistent with those of high-throughput sequencing.CONCLUSIONS ANK2p.F3067L is considered a novel and potentially pathogenic gene mutation in DCM.
基金This work was supported by Italian Ministery of Health RC 08C921 to LL,Istituto Auxologico Italiano,IRCCs.
文摘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.
基金National Natural Science Foundation of China(30972184,31272574).
文摘[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.
文摘以控制R om ney Inverdale绵羊和R om ney H anna绵羊高繁殖力的骨形态发生蛋白15(BM P 15)基因为候选基因,采用PCR-RFLP方法检测BM P 15基因在高繁殖力山羊品种(济宁青山羊)以及低繁殖力山羊品种(内蒙古绒山羊、安哥拉山羊、波尔山羊)中的多态性,同时研究该基因对济宁青山羊高繁殖力的影响。结果表明:BM P 15基因在济宁青山羊、内蒙古绒山羊、安哥拉山羊和波尔山羊中既未发生与Inverdale绵羊相同的V 31D突变,也未发生与H anna绵羊相同的Q 23T er突变。这表明BM P 15基因这2个突变位点对济宁青山羊的高繁殖力没有显著影响。
基金Department of Science & Technology,Ministry of Science & Technology,Government of India,for the award of Young Scientist Project(SR/FT/ L-111/2006)
文摘Objective:To delineate the frequency of occurrence of bla<sub>CTX-M</sub>,bla<sub>TEM</sub>,and bla<sub>SHV</sub> in Enterobacteriaceae from North-Indian tertiary hospital.Methods:A random collection of a subset of 45 Escherichia coli(E.coli) and 28 Klebsiella pneumoniae(K.pneumoniae) that was resistant to a third generation cephalosporin and obtained during 2007-2008 was selected for detailed screening for bla<sub>CTX-M</sub>,bla<sub>TEM</sub>,and bla<sub>SHV</sub> by monoplex PCRs.The isolates demonstrating the presence of bla<sub>CTX-M</sub> alleles were characterized for the specific CTX-M-genogroup by using a multiplex PCR.Results:Resistance to cefoperazone,ceftazidime,ceftriaxone,cefotaxime, cefoxitin and piperacillin was 100%each in K.pneumoniae isolates,whereas these resistancerates for E.coli isolates were 93.1%,83.8%,91.9%,93.6%,97.3%and 97.1%,respectively. Concomitant resistance to aminoglycosides,quinolones and aztreonam was also noticed.Presence of any of the bla genes(bla<sub>CTX-M</sub>,bla<sub>TEM</sub>,and bla<sub>SHV</sub>) was noticed in a total of 28(38.4%) isolates of the 73 isolates studied.Many isolates demonstrated occurrence of these genes in various combinations.bla<sub>CTX-M</sub>,bla<sub>TEM</sub>,and bla<sub>SHV</sub> were noticed in 28.8%,10.9%and 13.7%isolates, respectively.Multiplex PCR in bla<sub>CTX-M</sub> harboring isolates demonstrated the presence of CTX-MGenogroup -1 and sequencing for the specific CTX-M-type revealed presence of CTX-M-15 type. RAPD typing showed wide diversity in isolates.Conclusions:This is amongst the premier report describing the simultaneous occurrence of blo<sub>TEM</sub>,bla<sub>SHV</sub>,and bla<sub>ampC</sub> in Indian Enterobacteriaceae and that wider dissemination of these genes,as demonstrated by diversity of isolates,raises concern and emphasizes a need for extensive search for the presence of these gene pools in Indian subcontinent.
文摘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.
基金supported by the National Key Research and Development Program of China(2021YFD1200803)Sanya Yazhou Bay Science and Technology City Administration(SYND-2022-28)China Agriculture Research System of MOF and MARA(CARS-40).
文摘Background:Excessive abdominal fat deposition in commercial broilers presents an obstacle to profitable meat quality,feed utilization,and reproduction.Abdominal fat deposition depends on the proliferation of preadipocytes and their maturation into adipocytes,which involves a cascade of regulatory molecules.Accumulating evidence has shown that microRNAs(miRNAs)serve as post-transcriptional regulators of adipogenic differentiation in mammals.However,the miRNA-mediated molecular mechanisms underlying abdominal fat deposition in chickens are still poorly understood.This study aimed to investigate the biological functions and regulatory mechanism of miRNAs in chicken abdominal adipogenesis.Results:We established a chicken model of abdominal adipocyte differentiation and analyzed miRNA and mRNA expression in abdominal adipocytes at different stages of differentiation(0,12,48,72,and 120 h).A total of 217 differentially expressed miRNAs(DE-miRNAs)and 3520 differentially expressed genes were identified.Target prediction of DE-miRNAs and functional enrichment analysis revealed that the differentially expressed targets were significantly enriched in lipid metabolism-related signaling pathways,including the PPAR signaling and MAPK signaling pathways.A candidate miRNA,gga-miR-106-5p,exhibited decreased expression during the proliferation and differentiation of abdominal preadipocytes and was downregulated in the abdominal adipose tissues of fat chickens compared to that of lean chickens.gga-miR-106-5p was found to inhibit the proliferation and adipogenic differentiation of chicken abdominal preadipocytes.A dual-luciferase reporter assay suggested that the KLF15 gene,which encodes a transcriptional factor,is a direct target of gga-miR-106-5p.gga-miR-106-5p suppressed the posttranscriptional activity of KLF15,which is an activator of abdominal preadipocyte proliferation and differentiation,as determined with gain-and loss-of-function experiments.Conclusions:gga-miR-106-5p functions as an inhibitor of abdominal adipogenesis by targeting the KLF15 gene in chickens.These findings not only improve our understanding of the specific functions of miRNAs in avian adipogenesis but also provide potential targets for the genetic improvement of excessive abdominal fat deposition in poultry.
基金support by the Ministerio Educación y CienciaMinisterio de Economía y Competitividad of Spain(until June 2013)
文摘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.
文摘In the present experiment,an inhibitor of superoxide dismutase(SOD),diethyldithiocarbamate(DETC),was used to decrease SOD activity for the observation of the relation between SOD activity and carcinogenesis and the expression of P53 protein in vivo.144 Wistar rats were used for the Present study.The results showed that the SOD activity reduction by DETC resulted markedly in the promotion of the carcinogenesis and the expression of P53 protein in the lung tissues,but the increase of SOD activity by the addition of plus SOD inhibited the pathological changes significantly.The frequency of the pathological lesions and Positive P53 expression are 36/42 and 8/42 in the animals without DETC and SOD:16/52 and 4/52 in the animals with SOD and 46/50 and 26/50 in the animals with DETC respectively.The results reported in this Paper suggest that:(1) the decrease of SOD activity enhanced the carcinogenesis induced by chemical carcinogen;(2) P53 gene may be associated with the process of tumorigenesis;and(3) at the same time the abnormal expression of P53 protein may be associated with the transition from premalignant lesions to carcinoma.