AIM:To investigate H2B monoubiquitination(uH2B)and H3K4 di-and tri-methylation(H3K4-2me,H3K4-3me)levels and their clinical significance in gastric cancer(GC).METHODS:Immunohistochemistry(IGC)was used to detect the dif...AIM:To investigate H2B monoubiquitination(uH2B)and H3K4 di-and tri-methylation(H3K4-2me,H3K4-3me)levels and their clinical significance in gastric cancer(GC).METHODS:Immunohistochemistry(IGC)was used to detect the differential levels of uH2B,H3K4-2me and H3K4-3me modifications in GC specimens from chemo/radiotherapy-na ve patients who underwent potentially curative surgical resection(n=159)and in a random sampling of non-tumor gastric epithelium specimens(normal controls,n=20).The immunohistochemistry(IHC)-detected modifications were classified as negative,low-level,or high-level using a dual-rated(staining intensity and percentage of positively-stained cells)semi-quantitative method.The relationships between uH2B modification levels and clinicopathological parameters of GC were assessed by a Wilcoxon rank sum test(pairwise comparisons)and the Kruskal-Wallis H test(multiple comparisons).The correlation between uH2B modification and survival was estimated by Kaplan-Meier analysis,and the role of uH2B as an independent prognostic factor for survival was assessed by multivariate Cox regression analysis.RESULTS:The presence and level of H3K4-2me and H3K4-3me IHC staining was similar between the normal controls and GC specimens.In contrast,the level of uH2B was significantly lower in the malignant gastric tissues(vs normal control tissues)and decreased along with increases in dedifferentiation(well differentiated>moderately differentiated>poorly differentiated).The level of uH2B correlated with tumor differentiation(P<0.001),Lauren’s diffuse-and intestinal-type classification(P<0.001),lymph node metastasis(P=0.049)and tumor-node-metastasis stage(P=0.005).Patients with uH2B+staining had higher 5-year survival rates than patients with uH2B-staining(52.692±2.452 vs23.739±5.207,P<0.001).The uH2B level was an independent prognostic factor for cancer-specific survival(95%CI:0.237-0.677,P=0.001).CONCLUSION:uH2B displays differential IHC staining patterns corresponding to progressive stages of GC.uH2B may contribute to tumorigenesis and could be a potential therapeutic target.展开更多
In order to investigate molecular phylogenetic relationships of Drosophila immigransspecies group,nucleotide sequences of H2a-H2b spacer regions and partial nucleotide sequences of Cytochrome b gene for five specieses...In order to investigate molecular phylogenetic relationships of Drosophila immigransspecies group,nucleotide sequences of H2a-H2b spacer regions and partial nucleotide sequences of Cytochrome b gene for five specieses subgroup in Drosophila immigrans species group and D.hydei which was selected as outgroup were acquired. Phylogenetic trees were reconstructed using maximum parsimony,maximum likelihood,neighbor joining and Bayesian methods based on H2a-H2b and Cyt b DNA sequences. The results indicated that Drosophila curviceps species subgroup is located at the base of molecular trees, diverged first in this group; the second clade is Drosophila quadrilineata species subgroup; the third is Drosophila hypocausta species subgroup; the fourth is Drosophila immigrans species subgroup; Drosophila nasuta species subgroup is the last diverged clade. Moreover,the phylogentic relationships of seven specieses in Drosophila nasuta subgroup was investigated.展开更多
O-GlcNAcylation is an important post-translational modification and has been implicated in many fundamental cellular processes. Recent studies showed that O-linked N-acetylglucosamine （GlcNAc） transferase （OGT） me...O-GlcNAcylation is an important post-translational modification and has been implicated in many fundamental cellular processes. Recent studies showed that O-linked N-acetylglucosamine （GlcNAc） transferase （OGT） mediated O-GlcNAcylation of histone H2B Ser 112 （H2B S 112 GlcNAcylation） plays an important role in gene transcription. However, the role of this histone modification in DNA damage response has not been studied yet. In this study, we found that OGT and OGT mediated H2B S112 GlcNAcylation are involved in DNA damage response for maintaining genomic stability and are required for resistance to many DNA-damaging and replication stress- inducing agents. OGT mediated H2B Sl12 GlcNAcylation increased locally upon the induction of double-strand breaks （DSBs）, and depletion of OGT or overexpression of H2B S 112A mutant impaired homologous recombination （HR） and nonhomologous end-joining （NHEJ）. Mechanistically, H2B Sl12 GlcNAcylation could bind Nijmegen breakage syndrome 1 （NBS1） and regulate NBS1 foci for- mation. Taken together, our results demonstrate a new function of histone O-GlcNAcylation in DNA damage response （DDR）.展开更多
Autophagy is an evolutionarily conserved lysosome-mediated catabolic process（Klionsky,2007）.Autophagy is believed to be essential for cell survival,especially when cells were exposed to stresses,such as nutrient sta...Autophagy is an evolutionarily conserved lysosome-mediated catabolic process（Klionsky,2007）.Autophagy is believed to be essential for cell survival,especially when cells were exposed to stresses,such as nutrient starvation.展开更多
文摘目的探讨组蛋白H2B单泛素化(histone H2B monoubiquitination,u H2B)在原发性结肠腺癌中的表达及其与临床病理参数的关系。方法采用免疫组化ABC法检测116例原发性结肠腺癌及15例正常结肠黏膜组织中u H2B的表达,并复习相关文献。结果 u H2B在低分化原发性结肠腺癌中的阳性率(19.4%,6/31)显著低于高+中分化腺癌(49.4%,42/85)及正常结肠黏膜组织(86.7%,13/15),差异有统计学意义(P<0.05)。u H2B与肿瘤分化程度、Dukes分期、TNM分期及淋巴结转移相关(P<0.05),与患者性别、年龄无关(P>0.05)。结论 u H2B作为一种抑癌因子可能与原发性结肠腺癌的恶化过程密切相关。其可能会成为原发性结肠腺癌早期检测、治疗及预后评估的新分子生物学标志并应用于临床,而其在结肠腺癌中的具体作用机制仍有待进一步研究。
基金Supported by The Ministry of Science and Technology of China,No.2011CB966200 and 2013CB911000the National Natural Science Foundation of China,No.30970950,81071362,and 31171319+1 种基金the Program for Changjiang Scholars and Innovative Research Team in University of Ministry of Education of China,the Department of Science and Technology of Sichuan Province,No.2011SZ0002 and 2012JQ0005the Bureau of Science and Technology of Chengdu,No.11PPYB072SF
文摘AIM:To investigate H2B monoubiquitination(uH2B)and H3K4 di-and tri-methylation(H3K4-2me,H3K4-3me)levels and their clinical significance in gastric cancer(GC).METHODS:Immunohistochemistry(IGC)was used to detect the differential levels of uH2B,H3K4-2me and H3K4-3me modifications in GC specimens from chemo/radiotherapy-na ve patients who underwent potentially curative surgical resection(n=159)and in a random sampling of non-tumor gastric epithelium specimens(normal controls,n=20).The immunohistochemistry(IHC)-detected modifications were classified as negative,low-level,or high-level using a dual-rated(staining intensity and percentage of positively-stained cells)semi-quantitative method.The relationships between uH2B modification levels and clinicopathological parameters of GC were assessed by a Wilcoxon rank sum test(pairwise comparisons)and the Kruskal-Wallis H test(multiple comparisons).The correlation between uH2B modification and survival was estimated by Kaplan-Meier analysis,and the role of uH2B as an independent prognostic factor for survival was assessed by multivariate Cox regression analysis.RESULTS:The presence and level of H3K4-2me and H3K4-3me IHC staining was similar between the normal controls and GC specimens.In contrast,the level of uH2B was significantly lower in the malignant gastric tissues(vs normal control tissues)and decreased along with increases in dedifferentiation(well differentiated>moderately differentiated>poorly differentiated).The level of uH2B correlated with tumor differentiation(P<0.001),Lauren’s diffuse-and intestinal-type classification(P<0.001),lymph node metastasis(P=0.049)and tumor-node-metastasis stage(P=0.005).Patients with uH2B+staining had higher 5-year survival rates than patients with uH2B-staining(52.692±2.452 vs23.739±5.207,P<0.001).The uH2B level was an independent prognostic factor for cancer-specific survival(95%CI:0.237-0.677,P=0.001).CONCLUSION:uH2B displays differential IHC staining patterns corresponding to progressive stages of GC.uH2B may contribute to tumorigenesis and could be a potential therapeutic target.
文摘In order to investigate molecular phylogenetic relationships of Drosophila immigransspecies group,nucleotide sequences of H2a-H2b spacer regions and partial nucleotide sequences of Cytochrome b gene for five specieses subgroup in Drosophila immigrans species group and D.hydei which was selected as outgroup were acquired. Phylogenetic trees were reconstructed using maximum parsimony,maximum likelihood,neighbor joining and Bayesian methods based on H2a-H2b and Cyt b DNA sequences. The results indicated that Drosophila curviceps species subgroup is located at the base of molecular trees, diverged first in this group; the second clade is Drosophila quadrilineata species subgroup; the third is Drosophila hypocausta species subgroup; the fourth is Drosophila immigrans species subgroup; Drosophila nasuta species subgroup is the last diverged clade. Moreover,the phylogentic relationships of seven specieses in Drosophila nasuta subgroup was investigated.
基金supported by the grants from the National Program on Key Basic Research Project (Nos. 2013CB910300 and 2012CB910300 to H.P.)the International Science and Technology Cooperation Program of China (No. 2015DFA31680)+2 种基金the One Thousand Young Talent Program (to H.P.)the State Key Laboratory of Proteomics (No. SKLP-O201303 to C.Y.)the National Natural Science Foundation of China (No. 31371433 to H.P.)
文摘O-GlcNAcylation is an important post-translational modification and has been implicated in many fundamental cellular processes. Recent studies showed that O-linked N-acetylglucosamine （GlcNAc） transferase （OGT） mediated O-GlcNAcylation of histone H2B Ser 112 （H2B S 112 GlcNAcylation） plays an important role in gene transcription. However, the role of this histone modification in DNA damage response has not been studied yet. In this study, we found that OGT and OGT mediated H2B S112 GlcNAcylation are involved in DNA damage response for maintaining genomic stability and are required for resistance to many DNA-damaging and replication stress- inducing agents. OGT mediated H2B Sl12 GlcNAcylation increased locally upon the induction of double-strand breaks （DSBs）, and depletion of OGT or overexpression of H2B S 112A mutant impaired homologous recombination （HR） and nonhomologous end-joining （NHEJ）. Mechanistically, H2B Sl12 GlcNAcylation could bind Nijmegen breakage syndrome 1 （NBS1） and regulate NBS1 foci for- mation. Taken together, our results demonstrate a new function of histone O-GlcNAcylation in DNA damage response （DDR）.
基金supported by the National Basic Research Program of China (973 Program)(No.2016YFA0100400)the National Natural Science Foundation of China(No.81773009)
文摘Autophagy is an evolutionarily conserved lysosome-mediated catabolic process（Klionsky,2007）.Autophagy is believed to be essential for cell survival,especially when cells were exposed to stresses,such as nutrient starvation.
