Single-molecule, real-time sequencing developed by Pacific BioSciences offers longer read lengths than the second-generation sequencing （SGS） technologies, making it well-suited for unsolved problems in genome, tran...Single-molecule, real-time sequencing developed by Pacific BioSciences offers longer read lengths than the second-generation sequencing （SGS） technologies, making it well-suited for unsolved problems in genome, transcriptome, and epigenetics research. The highly-contiguous de novo assemblies using PacBio sequencing can close gaps in current reference assemblies and characterize structural variation （SV） in personal genomes. With longer reads, we can sequence through extended repetitive regions and detect mutations, many of which are associated with dis- eases. Moreover, PacBio transcriptome sequencing is advantageous for the identification of gene isoforms and facilitates reliable discoveries of novel genes and novel isoforms of annotated genes, due to its ability to sequence full-length transcripts or fragments with significant lengths. Addition- ally, PacBio＇s sequencing technique provides information that is useful for the direct detection of base modifications, such as methylation. In addition to using PacBio sequencing alone, many hybrid sequencing strategies have been developed to make use of more accurate short reads in conjunction with PacBio long reads. In general, hybrid sequencing strategies are more affordable and scalable especially for small-size laboratories than using PacBio Sequencing alone. The advent of PacBio sequencing has made available much information that could not be obtained via SGS alone.展开更多
The development and progression of gastric cancer involves a number of genetic and epigenetic alterations of tumor suppressor and tumor-related genes. The majority of differentiated carcinomas arise from intestinal me...The development and progression of gastric cancer involves a number of genetic and epigenetic alterations of tumor suppressor and tumor-related genes. The majority of differentiated carcinomas arise from intestinal metaplastic mucosa and exhibit structurally altered tumor suppressor genes, typified by p53, which is inactivated via the classic two-hit mechanism, i.e. loss of heterozygosity （LOH） and mutation of the remaining allele. LOH at certain chromosomal loci accumulates during tumor progression. Approximately 20% of differentiated carcinomas show evidence of mutator pathway tumorigenesis due to hMLH1 inactivation via hypermethylation of promoter CpG islands, and exhibit high-frequency microsatellite instability. In contrast, undifferentiated carcinomas rarely exhibit structurally altered tumor suppressor genes. For instance, while methylation of E-cadherin is often observed in undifferentiated carcinomas, mutation of this gene is generally associated with the progression from differentiated to undifferentiated carcinomas. Hypermethylation of tumor suppressor and tumor-related genes, including APC, CHFR, DAP- kinase, DCC, E-cadherin, GSTP1, hMLH1, p16, PTEN, RASSF1A, RUNX3, and TSLC1, can be detected in both differentiated and undifferentiated carcinomas at varying frequencies. However, the significance of the hypermethylation varies according to the analyzed genomic region, and hypermethylation of these genes can also be present in non-neoplastic gastric epithelia. Promoter demethylation of specific genes, such as MAGE and synudein y, can occur during the progressive stages of both histological types, and is associated with patient prognosis. Thus, while the molecular pathways of gastric carcinogenesis are dependent on histological background, specific genetic alterations can still be used for risk assessment, diagnosis, and prognosis.展开更多
AIM： TO determine p15 promoter hypermethylation in gastric tumoral tissue and serum samples, its impact on p16-protein expression, and correlation with clinical and histological features. METHODS： Samples were obtai...AIM： TO determine p15 promoter hypermethylation in gastric tumoral tissue and serum samples, its impact on p16-protein expression, and correlation with clinical and histological features. METHODS： Samples were obtained from 52 histologically confirmed cases of gastric adenocarcinoma. Gastric tissue and serum of 50 age- and sex-matched individuals with normal gastroscopy and biopsy were obtained as control samples. Methylation-specific polymerase chain reaction （MSP） was used to evaluate methylation status of p16 promoter, p16-protein expression was analyzed by immunohistochemical staining on paraffin-embedded sections. RESULTS： Methylation was detected in 44.2% （23/52） of tumoral tissues. 60.9% of them were also methylated in serum, i.e., 26.9% of all patients （14/52）. Methylation was not detected in tissue and sera of control samples. p16-protein expression was decreased in 61.5% of cases （32/52）, and was significantly associated with promoter hypermethylation （P 〈 0.001）. Methylation was significantly more frequent in higher pathological grades （P 〈 0.05）. Methylation was not associated with other clinicopathological features and environmental factors including Hpylori infection and smoking. CONCLUSION： p16 promoter hypermethylation is an important event in gastric carcinogenesis. It is the principle mechanism of p16 gene silencing. It is related to malignant tumor behavior. Detection of DNA methylation in serum may be a biomarker for early detection of gastric cancer.展开更多
AIM: To determine if gene-specific DNA methylation in prospectively collected blood samples is associated with later development of hepatocellular carcinoma(HCC).METHODS: Comparing genome-wide DNA methylation profiles...AIM: To determine if gene-specific DNA methylation in prospectively collected blood samples is associated with later development of hepatocellular carcinoma(HCC).METHODS: Comparing genome-wide DNA methylation profiles using Illumina Human methylation 450 K arrays, we previously identified a list of loci that were differentially methylated between tumor and adjacent nontumor tissues. To examine if dysregulation of DNAmethylation patterns observed in tumor tissues can be detected in white blood cell(WBC) DNA, we conducted a prospective case-control study nested within a community-based cancer screening cohort in Taiwan with 16 years of follow up. We measured methylation levels in ninety-six loci that were aberrant in DNA methylation in HCC tumor tissues compared to adjacent tissues. Baseline WBC DNA from 159 HCC cases and 312 matched controls were bisulfite treated and assayed by Illumina Bead Array. We used the χ2 test for categorical variables and student's t-test for continuous variables to assess the difference in selected characteristics between cases and controls. To estimate associations with HCC risk, we used conditional logistic regression models stratified on the matching factors to calculate odds ratios(OR) and 95%CI. RESULTS: We found that high methylation level in cg10272601 in WNK2 was associated with increased risk of HCC, with an OR of 1.91(95%CI: 1.27-2.86). High methylation levels in both cg12680131 in TPO and cg22511877 in MYT1 L, however, were associated with decreased risk. The ORs(95%CI) were 0.59(0.39-0.87) and 0.50(0.33-0.77), respectively, for those with methylation levels of cg12680131 and cg22511877 above the median compared with those with levels below the median. These associations were still statistically significant in multivariable conditional logistic regression models after adjusting for hepatitis B virus infection and alcohol consumption. CONCLUSION: These findings support the measurement of methylation markers in WBC DNA as biomarkers of HCC susceptibility but should be replicat展开更多
The aim of this study is to assess the effects of DNA methylation and historic acetylation, alone or in combination, on the expression of several tumor-associated genes and cell cycle progression in two established hu...The aim of this study is to assess the effects of DNA methylation and historic acetylation, alone or in combination, on the expression of several tumor-associated genes and cell cycle progression in two established human colon cancer cell lines: Colo-320 and SW1116. Treatments with 5-aza-2'-deoxycytidine (5-aza-dC) and trichostatin A, alone or in combination, were applied respectively. The methylation status of the CDKN2A promoter was determined by methyla-tion-specific PCR, and the acetylated status of the histones associated with the p21WAF1 and CDKN2A genes was examined by chromatin immunoprecipitation. The expression of the CDKN2A, p21WAF1, p53, p73, APC, c-myc, c-Ki-ras and survivin genes was detected by real-time RT-PCR and RT-PCR. The cell cycle profile was established by flow cytometry. We found that along with the demethylation of the CDKN2A gene promoter in both cell lines induced by 5-aza-dC alone or in combination with TSA, the expression of both CDKN2A and APC genes increased. The treatment of TSA or sodium butyrate up-regulated the transcription of p21WAF1 significantly by inducing the acetylation of histones H4 and H3, but failed to alter the acetylation level of CDKN2A-associated histones. No changes in transcription of p53, p73, c-myc, c-Ki-ras and survivin genes were observed. In addition, TSA or sodium butyrate was shown to arrest cells at the G1 phase. However, 5-aza-dC was not able to affect the cell cycle progression. In conclusion, regulation by epigenetic modification of the transcription of tumor-associated genes and the cell cycle progression in both human colon cancer cell lines Colo-320 and SW1116 is gene-specific.展开更多
Abscisic acid （ABA） regulates diverse plant processes, growth and development under non-stress conditions and plays a pivotal role in abiotic stress tolerance. Although ABA-regulated genetic processes are well known...Abscisic acid （ABA） regulates diverse plant processes, growth and development under non-stress conditions and plays a pivotal role in abiotic stress tolerance. Although ABA-regulated genetic processes are well known, recent discoveries reveal that epigenetic processes are an integral part of ABA-regulated processes. Epigenetic mechanisms, namely, histone modifications and cytosine DNA methylation-induced modification of genome give rise to epigenomes, which add diversity and complexity to the genome of organisms. Histone monoubiquitination appears to regulate ABA levels in developing seeds through histone H2B monoubiquitination. ABA and H2B ubiquitination dependent chromatin remodeling regulate seed dormancy. Transcription factor networks necessary for seed maturation are repressed by histone deacetylases （HDACs）-dependent and PICKLE chromatin remodeling complexes （CRCs）, whereas ABA induces the expression of these genes directly or through repression of HDACs. Abiotic stress-induced ABA regulates stomatal response and stress- responsive gene expression through HDACs and HOS15-dependent histone deacetylation, as well as through the ATP- dependent SWITCH/SUCROSE NONFERMENTING CRC. ABA also probably regulates the abiotic stress response through DNA methylation and short interfering RNA pathways. Further studies on ABA-regulated epigenome will be of immense use to understand the plant development, stress adaptation and stress memory.展开更多
Like protein and DNA, different types of RNA molecules undergo various modifications. Accumulating evidence suggests that these RNA modifications serve as sophisticated codes to mediate RNA behaviors and many importan...Like protein and DNA, different types of RNA molecules undergo various modifications. Accumulating evidence suggests that these RNA modifications serve as sophisticated codes to mediate RNA behaviors and many important biological functions. N^6-methyladenosine （m^6A） is the most abundant internal RNA modification found in a variety of eukaryotic RNAs, including but not limited to mRNAs, tRNAs, rRNAs, and long non-coding RNAs （lncRNAs）. In mammalian cells, m^6A can be incorporated by a methyltransferase complex and removed by demethy- lases, which ensures that the m^6A modification is reversible and dynamic. Moreover, m^6A is recognized by the YT521-B homology （YTH） domain-containing proteins, which subsequently direct different complexes to regulate RNA signaling pathways, such as RNA metabolism, RNA splicing, RNA folding, and protein translation. Herein, we summarize the recent progresses made in understanding the molecular mechanisms underlying the m^6A recognition by YTH domaincontaining proteins, which would shed new light on m^6A-specific recognition and provide clues to the future identification of reader proteins of many other RNA modifications.展开更多
To determine the possible role of the epigenetic mechanisms in carcinogenesis of the hepatocellular carcinoma, we methylation-profiled the promoter CpG islands of twenty four genes both in HCC tumors and the neighbori...To determine the possible role of the epigenetic mechanisms in carcinogenesis of the hepatocellular carcinoma, we methylation-profiled the promoter CpG islands of twenty four genes both in HCC tumors and the neighboring non-cancerous tissues of twenty eight patients using the methylation-specific PCR (MSP) method in conjunction with the DNA sequencing. In comparison with the normal liver tissues from the healthy donors, it was found that while remained unmethylated the ABL, CAV, EPO, GATA3, LKB1, NEP, NFL, NIS and p27^(KIP1) genes, varying extents of the HCC specific hypermethylation were found associated with the ABO, AR, CSPG2, cyclin al, DBCCR1, GALR2, IRF7, MGMT, MT1A, MYOD1, OCT6, p57^(KIP2), p73, WT1 genes, and demethylation with the MAGEA1 gene, respectively. Judged by whether the hypermethylated occurred in HCC more frequently than in their neighboring normal tissues, the hypermethylation status of the AR, DBCCR1, IRF7, OCT6, and p73 genes was considered as the event specific to the late stage, while that the rest that lacked such a distinguished contrast, as the event specific to the early stage of HCC carcinogenesis. Among all the clinical pathological parameters tested for the association with, the hypermethylation of the cyclin al gene was more prevalent in the non-cirrhosis group (P=0.021) while the hypermethylated p16^(INK4a) gene was more common in the cirrhosis group (P=0.017). The concordant methylation behaviors of nineteen genes, including the four previously studied and their association with cirrhosis has been evaluated by the best subgroup selection method. The data presented in this report would enable us to shape our understanding of the mechanisms for the HCC specific loss of the epigenetic stability of the genome, as well as the strategy of developing the novel robust methylation based diagnostic and prognostic tools.展开更多
14-3-3 is a highly conserved acidic protein family, composed of seven isoforms in mammals. 14-3-3 protein caninteract with over 200 target proteins by phosphoserine-dependent and phosphoserine-independent manners. Lit...14-3-3 is a highly conserved acidic protein family, composed of seven isoforms in mammals. 14-3-3 protein caninteract with over 200 target proteins by phosphoserine-dependent and phosphoserine-independent manners. Little isknown about the consequences of these interactions, and thus are the subjects of ongoing studies. 14-3-3 controls cellcycle, cell growth, differentiation, survival, apoptosis, migration and spreading. Recent studies have revealed newmechanisms and new functions of 14-3-3, giving us more insights on this fascinating and complex family of proteins.Of all the seven isoforms, 14-3-3σ seems to be directly involved in human cancer. 14-3-3σ itself is subject to regulationby p53 upon DNA damage and by epigenetic deregulation. Gene silencing of 14-3-3σ by CpG methylation has beenfound in many human cancer types. This suggests that therapy-targeting 14-3-3σ may be beneficial for future cancertreatment.展开更多
基金supported by the institutional fund of the Department of Internal Medicine, University of Iowa, USA
文摘Single-molecule, real-time sequencing developed by Pacific BioSciences offers longer read lengths than the second-generation sequencing （SGS） technologies, making it well-suited for unsolved problems in genome, transcriptome, and epigenetics research. The highly-contiguous de novo assemblies using PacBio sequencing can close gaps in current reference assemblies and characterize structural variation （SV） in personal genomes. With longer reads, we can sequence through extended repetitive regions and detect mutations, many of which are associated with dis- eases. Moreover, PacBio transcriptome sequencing is advantageous for the identification of gene isoforms and facilitates reliable discoveries of novel genes and novel isoforms of annotated genes, due to its ability to sequence full-length transcripts or fragments with significant lengths. Addition- ally, PacBio＇s sequencing technique provides information that is useful for the direct detection of base modifications, such as methylation. In addition to using PacBio sequencing alone, many hybrid sequencing strategies have been developed to make use of more accurate short reads in conjunction with PacBio long reads. In general, hybrid sequencing strategies are more affordable and scalable especially for small-size laboratories than using PacBio Sequencing alone. The advent of PacBio sequencing has made available much information that could not be obtained via SGS alone.
文摘The development and progression of gastric cancer involves a number of genetic and epigenetic alterations of tumor suppressor and tumor-related genes. The majority of differentiated carcinomas arise from intestinal metaplastic mucosa and exhibit structurally altered tumor suppressor genes, typified by p53, which is inactivated via the classic two-hit mechanism, i.e. loss of heterozygosity （LOH） and mutation of the remaining allele. LOH at certain chromosomal loci accumulates during tumor progression. Approximately 20% of differentiated carcinomas show evidence of mutator pathway tumorigenesis due to hMLH1 inactivation via hypermethylation of promoter CpG islands, and exhibit high-frequency microsatellite instability. In contrast, undifferentiated carcinomas rarely exhibit structurally altered tumor suppressor genes. For instance, while methylation of E-cadherin is often observed in undifferentiated carcinomas, mutation of this gene is generally associated with the progression from differentiated to undifferentiated carcinomas. Hypermethylation of tumor suppressor and tumor-related genes, including APC, CHFR, DAP- kinase, DCC, E-cadherin, GSTP1, hMLH1, p16, PTEN, RASSF1A, RUNX3, and TSLC1, can be detected in both differentiated and undifferentiated carcinomas at varying frequencies. However, the significance of the hypermethylation varies according to the analyzed genomic region, and hypermethylation of these genes can also be present in non-neoplastic gastric epithelia. Promoter demethylation of specific genes, such as MAGE and synudein y, can occur during the progressive stages of both histological types, and is associated with patient prognosis. Thus, while the molecular pathways of gastric carcinogenesis are dependent on histological background, specific genetic alterations can still be used for risk assessment, diagnosis, and prognosis.
基金A grant offered by Mashhad University of Medical Sciences, No. 84129
文摘AIM： TO determine p15 promoter hypermethylation in gastric tumoral tissue and serum samples, its impact on p16-protein expression, and correlation with clinical and histological features. METHODS： Samples were obtained from 52 histologically confirmed cases of gastric adenocarcinoma. Gastric tissue and serum of 50 age- and sex-matched individuals with normal gastroscopy and biopsy were obtained as control samples. Methylation-specific polymerase chain reaction （MSP） was used to evaluate methylation status of p16 promoter, p16-protein expression was analyzed by immunohistochemical staining on paraffin-embedded sections. RESULTS： Methylation was detected in 44.2% （23/52） of tumoral tissues. 60.9% of them were also methylated in serum, i.e., 26.9% of all patients （14/52）. Methylation was not detected in tissue and sera of control samples. p16-protein expression was decreased in 61.5% of cases （32/52）, and was significantly associated with promoter hypermethylation （P 〈 0.001）. Methylation was significantly more frequent in higher pathological grades （P 〈 0.05）. Methylation was not associated with other clinicopathological features and environmental factors including Hpylori infection and smoking. CONCLUSION： p16 promoter hypermethylation is an important event in gastric carcinogenesis. It is the principle mechanism of p16 gene silencing. It is related to malignant tumor behavior. Detection of DNA methylation in serum may be a biomarker for early detection of gastric cancer.
文摘AIM: To determine if gene-specific DNA methylation in prospectively collected blood samples is associated with later development of hepatocellular carcinoma(HCC).METHODS: Comparing genome-wide DNA methylation profiles using Illumina Human methylation 450 K arrays, we previously identified a list of loci that were differentially methylated between tumor and adjacent nontumor tissues. To examine if dysregulation of DNAmethylation patterns observed in tumor tissues can be detected in white blood cell(WBC) DNA, we conducted a prospective case-control study nested within a community-based cancer screening cohort in Taiwan with 16 years of follow up. We measured methylation levels in ninety-six loci that were aberrant in DNA methylation in HCC tumor tissues compared to adjacent tissues. Baseline WBC DNA from 159 HCC cases and 312 matched controls were bisulfite treated and assayed by Illumina Bead Array. We used the χ2 test for categorical variables and student's t-test for continuous variables to assess the difference in selected characteristics between cases and controls. To estimate associations with HCC risk, we used conditional logistic regression models stratified on the matching factors to calculate odds ratios(OR) and 95%CI. RESULTS: We found that high methylation level in cg10272601 in WNK2 was associated with increased risk of HCC, with an OR of 1.91(95%CI: 1.27-2.86). High methylation levels in both cg12680131 in TPO and cg22511877 in MYT1 L, however, were associated with decreased risk. The ORs(95%CI) were 0.59(0.39-0.87) and 0.50(0.33-0.77), respectively, for those with methylation levels of cg12680131 and cg22511877 above the median compared with those with levels below the median. These associations were still statistically significant in multivariable conditional logistic regression models after adjusting for hepatitis B virus infection and alcohol consumption. CONCLUSION: These findings support the measurement of methylation markers in WBC DNA as biomarkers of HCC susceptibility but should be replicat
基金This work was supported in part by National Natural Science Foundation of China(No.30170413)the Foundation for Jing Yuan FANG of National Excellent Doctoral Dissertation of China(No.199946)the Foundation of Shanghai Education Committee(Shuguang Plan,No.02SG45).
文摘The aim of this study is to assess the effects of DNA methylation and historic acetylation, alone or in combination, on the expression of several tumor-associated genes and cell cycle progression in two established human colon cancer cell lines: Colo-320 and SW1116. Treatments with 5-aza-2'-deoxycytidine (5-aza-dC) and trichostatin A, alone or in combination, were applied respectively. The methylation status of the CDKN2A promoter was determined by methyla-tion-specific PCR, and the acetylated status of the histones associated with the p21WAF1 and CDKN2A genes was examined by chromatin immunoprecipitation. The expression of the CDKN2A, p21WAF1, p53, p73, APC, c-myc, c-Ki-ras and survivin genes was detected by real-time RT-PCR and RT-PCR. The cell cycle profile was established by flow cytometry. We found that along with the demethylation of the CDKN2A gene promoter in both cell lines induced by 5-aza-dC alone or in combination with TSA, the expression of both CDKN2A and APC genes increased. The treatment of TSA or sodium butyrate up-regulated the transcription of p21WAF1 significantly by inducing the acetylation of histones H4 and H3, but failed to alter the acetylation level of CDKN2A-associated histones. No changes in transcription of p53, p73, c-myc, c-Ki-ras and survivin genes were observed. In addition, TSA or sodium butyrate was shown to arrest cells at the G1 phase. However, 5-aza-dC was not able to affect the cell cycle progression. In conclusion, regulation by epigenetic modification of the transcription of tumor-associated genes and the cell cycle progression in both human colon cancer cell lines Colo-320 and SW1116 is gene-specific.
基金SERC Fact Track Scheme for Young Scientist, DST, Govt.of India, New Delhi to V. Chinnusamythe State Key Basic Researchand Development Plan of China (2003CB114300)the National Natural Science Foundation of China (30421002 and 30670182) to Z. Gong.
文摘Abscisic acid （ABA） regulates diverse plant processes, growth and development under non-stress conditions and plays a pivotal role in abiotic stress tolerance. Although ABA-regulated genetic processes are well known, recent discoveries reveal that epigenetic processes are an integral part of ABA-regulated processes. Epigenetic mechanisms, namely, histone modifications and cytosine DNA methylation-induced modification of genome give rise to epigenomes, which add diversity and complexity to the genome of organisms. Histone monoubiquitination appears to regulate ABA levels in developing seeds through histone H2B monoubiquitination. ABA and H2B ubiquitination dependent chromatin remodeling regulate seed dormancy. Transcription factor networks necessary for seed maturation are repressed by histone deacetylases （HDACs）-dependent and PICKLE chromatin remodeling complexes （CRCs）, whereas ABA induces the expression of these genes directly or through repression of HDACs. Abiotic stress-induced ABA regulates stomatal response and stress- responsive gene expression through HDACs and HOS15-dependent histone deacetylation, as well as through the ATP- dependent SWITCH/SUCROSE NONFERMENTING CRC. ABA also probably regulates the abiotic stress response through DNA methylation and short interfering RNA pathways. Further studies on ABA-regulated epigenome will be of immense use to understand the plant development, stress adaptation and stress memory.
基金supported by the National Natural Science Foundation of China awarded to SL(Grant No.31500601)and CX(Grants Nos.31570737 and 31770806)supported by the“1000 Young Talents Program”of China
文摘Like protein and DNA, different types of RNA molecules undergo various modifications. Accumulating evidence suggests that these RNA modifications serve as sophisticated codes to mediate RNA behaviors and many important biological functions. N^6-methyladenosine （m^6A） is the most abundant internal RNA modification found in a variety of eukaryotic RNAs, including but not limited to mRNAs, tRNAs, rRNAs, and long non-coding RNAs （lncRNAs）. In mammalian cells, m^6A can be incorporated by a methyltransferase complex and removed by demethy- lases, which ensures that the m^6A modification is reversible and dynamic. Moreover, m^6A is recognized by the YT521-B homology （YTH） domain-containing proteins, which subsequently direct different complexes to regulate RNA signaling pathways, such as RNA metabolism, RNA splicing, RNA folding, and protein translation. Herein, we summarize the recent progresses made in understanding the molecular mechanisms underlying the m^6A recognition by YTH domaincontaining proteins, which would shed new light on m^6A-specific recognition and provide clues to the future identification of reader proteins of many other RNA modifications.
基金supported by the National High Technology Research and Development Program of China(863 Program)(2001AA217011,2002AA2Z3352)the Major State Basic Research Development Program of China (973 Program)(G1998051004)the Science Foundation of Shanghai Municipal Government(02DJ14056)to JingDe ZHU.
文摘To determine the possible role of the epigenetic mechanisms in carcinogenesis of the hepatocellular carcinoma, we methylation-profiled the promoter CpG islands of twenty four genes both in HCC tumors and the neighboring non-cancerous tissues of twenty eight patients using the methylation-specific PCR (MSP) method in conjunction with the DNA sequencing. In comparison with the normal liver tissues from the healthy donors, it was found that while remained unmethylated the ABL, CAV, EPO, GATA3, LKB1, NEP, NFL, NIS and p27^(KIP1) genes, varying extents of the HCC specific hypermethylation were found associated with the ABO, AR, CSPG2, cyclin al, DBCCR1, GALR2, IRF7, MGMT, MT1A, MYOD1, OCT6, p57^(KIP2), p73, WT1 genes, and demethylation with the MAGEA1 gene, respectively. Judged by whether the hypermethylated occurred in HCC more frequently than in their neighboring normal tissues, the hypermethylation status of the AR, DBCCR1, IRF7, OCT6, and p73 genes was considered as the event specific to the late stage, while that the rest that lacked such a distinguished contrast, as the event specific to the early stage of HCC carcinogenesis. Among all the clinical pathological parameters tested for the association with, the hypermethylation of the cyclin al gene was more prevalent in the non-cirrhosis group (P=0.021) while the hypermethylated p16^(INK4a) gene was more common in the cirrhosis group (P=0.017). The concordant methylation behaviors of nineteen genes, including the four previously studied and their association with cirrhosis has been evaluated by the best subgroup selection method. The data presented in this report would enable us to shape our understanding of the mechanisms for the HCC specific loss of the epigenetic stability of the genome, as well as the strategy of developing the novel robust methylation based diagnostic and prognostic tools.
文摘14-3-3 is a highly conserved acidic protein family, composed of seven isoforms in mammals. 14-3-3 protein caninteract with over 200 target proteins by phosphoserine-dependent and phosphoserine-independent manners. Little isknown about the consequences of these interactions, and thus are the subjects of ongoing studies. 14-3-3 controls cellcycle, cell growth, differentiation, survival, apoptosis, migration and spreading. Recent studies have revealed newmechanisms and new functions of 14-3-3, giving us more insights on this fascinating and complex family of proteins.Of all the seven isoforms, 14-3-3σ seems to be directly involved in human cancer. 14-3-3σ itself is subject to regulationby p53 upon DNA damage and by epigenetic deregulation. Gene silencing of 14-3-3σ by CpG methylation has beenfound in many human cancer types. This suggests that therapy-targeting 14-3-3σ may be beneficial for future cancertreatment.
