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Long noncoding RNA-H19promotes proliferation and Epithelial-Mesenchymal transition through a myc-related feedback loop during liver regeneration in mice

Long noncoding RNA-H19promotes proliferation and Epithelial-...

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中华医学会2012年医学遗传学年会暨全国第十一次医学遗传学学术会议

作者：王芳杨富徐丹袁继行张铃孙树汉第二军医大学医学遗传学教研室上海200433

Liver regeneration driven by hepatocyte proliferation is necessary for tissue repair and survival after acute liver injury,liver transplantation,and chronic hepatic *** a partial hepatectomy(PHx)in mice,a rapid induction of proliferative factors activates quiescent hepatocytes and primes their subsequent *** this process,many transcription factors are activated and up-regulate a large number of proliferation-related target genes to repair the liver.c-Myc is a central transcription factor and is essential for total liver *** up-regulation of c-myc mRNA occurs 30 minutes after PHx and sharply increases after several ***,the mechanism of the fast up-regulation of c-myc in early liver regeneration remains *** this study,we reported for the first time that a c-myc-related positive feedback loop contributed to this phenomenon.A long noncoding RNA(lncRNA),H19,stabilized the c-myc mRNA by forming a H19-hnRNP U-myc complex and was transcriptionally up-regulated by c-myc in liver *** many microRNAs,which are a type of noncoding RNA,have been reported to control liver regeneration,H19 is the first lncRNA that is involved in liver *** also found that H19 promotes an epithelial-to-mesenchymal transition(EMT)in liver cells during ***:lncRNA-H19 promotes hepatocyte proliferation and EMT by stabilizing c-myc mRNA in early liver ***,the existence of a c-myc-related positive feedback loop augmented the effect of c-myc for a short time period during early liver regeneration.

关键词： long noncoding RNA hnRNP U partial hepatectomy RNA-protein complex epithelial-mesenchymal transition

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UBE2C在斑马鱼胚胎发育过程中的功能研究

UBE2C在斑马鱼胚胎发育过程中的功能研究

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2014全球华人遗传学大会暨全国第十三次医学遗传学学术会议

作者：胡月阳王芳张铃刘峰刘超谢英张力王鹏飞郑龙刘树锋王俊霞河北医科大学分子生物学研究室河北省实验动物实验室第二军医大学医学遗传学教研室

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The"c-Myc/miR-15-16/FGF2"axis plays an important role in hypoxia-induced distant tumor metastasis

The"c-Myc/miR-15-16/FGF2"axis plays an important role in hyp...

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中华医学会2012年医学遗传学年会暨全国第十一次医学遗传学学术会议

作者：薛赓颜宏利张毅单石孙树汉第二军医大学基础医学部医学遗传学教研室上海200433

Previous studies have established the link between aberrant microRNA(miRNA)level and hypoxia in various ***,how these aberrant miRNAs induced by hypoxia modulate tumor progression is still *** this study,the miRNA patterns of colorectal carcinoma(CRC)cells in hypoxia were screened by a high-resolution miRNA microarray and the hypoxia-induced repression of miR-15-16 was *** repression was associated with higher tumor stage and poor prognosis in *** was further disclosed that the hypoxia-induced repression of miR-15-16 promoted angiogenesis and metastasis by the loss of post-transcriptional inhibition of fibroblast growth factor-2(FGF2),Moreover,the promoter of the host gene (deleted in lymphocytic leukemia 2,DLEU2)of the miR-15-16 cluster was mapped and three Myc/Max binding sites responding in hypoxia were ***,the transcriptional repression of c-Myc to miR-15-16 via these Myc/Max binding sites in hypoxia was ***,we verified that the functional "c-Myc/miR-15-16/FGF2"pathway would play an important role in hypoxia-induced distant tumor *** a word,c-Myc-mediated repression of the miR-15-16 cluster in hypoxia promotes tumor angiogenesis and distant metastasis by upregulating *** study provides a better understanding of the coping mechanisms of microRNAs in response to hypoxia and may be helpful in developing more effective prognostic markers or treatment targets for solid tumors.

关键词： c-Myc fibroblast growth factor-2 hypoxia metastasis miR-15-1

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卡介菌基因组DNA的制备及其免疫调控活性研究

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河北医科大学学报 2009年第11期30卷 1163-1166页

作者：王静霍树平左连富孙树汉河北医科大学第四医院肿瘤研究所流式分析室河北医科大学第三医院麻醉科第二军医大学医学遗传学教研室

目的探索一种利用离子交换层析技术制备高纯度卡介菌基因组DNA(genomic DNA frommycobacterium bovis Bacillus calmette-Guerin,BCG-DNA)的方法,并探讨其免疫调控活性。方法运用超声、加热、胰酶消化、离子交换层析、凝胶过滤层析及冻... 详细信息

目的探索一种利用离子交换层析技术制备高纯度卡介菌基因组DNA(genomic DNA frommycobacterium bovis Bacillus calmette-Guerin,BCG-DNA)的方法,并探讨其免疫调控活性。方法运用超声、加热、胰酶消化、离子交换层析、凝胶过滤层析及冻干法制备高纯度BCG-DNA;小鼠脾细胞与BCG-DNA共同培养72h,采用ELISA方法检测细胞培养上清中干扰素γ(interferon-γ,IFN-γ)的水平。结果所制备的BCG-DNA纯度较高(DNA 95.3%),片断大小均匀一致,集中于200～250bp;BCG DNA可显著诱导小鼠脾细胞产生IFN γ(P<0.01),且IFN-γ水平与BCG-DNA浓度呈正相关。结论利用层析法制备BCG-DNA,高效、重复性好。所制备的BCG-DNA纯度较高,具有较强的免疫调控作用。

关键词：分枝杆菌,牛基因组提取法小鼠

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DNA Methylomes in CpG Island Methylator Phenotype(CIMP)Colon Cancer:new screening marks proposal

DNA Methylomes in CpG Island Methylator Phenotype(CIMP)Colon...

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中华医学会2012年医学遗传学年会暨全国第十一次医学遗传学学术会议

作者：颜宏利唐冠楠章意亮王玉招孙树汉第二军医大学基础医学部医学遗传学教研室上海200433

DNA methylation is essential for normal development and is frequently altered in *** Island Methylator Phenotype(CIMP)is a subset of colorectal cancers was postulated to have a higher propensity for DNA ***,the validity of CIMP,its molecular basis,and its prognostic values are highly *** aims of this study were to(1)compare and characterize the unique features of DNA methylomes of CIMP with Non-CIMP colonrectal cancers;(2)propose a new panel of valuable markers for CIMP *** we utilized MBD-isolated Genome Sequencing(MiGS)to map the DNA methylomes of three sets of normal colon,non-CIMP colon cancers,and CIMP colon *** regions only robust hypermethylated in CIMP tumors were evaluated in 120 colorectal tumors by Bisulfite genomic sequencing or Methylation Specific PCR(MSP).We found 4,800 sites were hypermethylated in both non-CIMP and CIMP colon cancers when compared with normal *** those sites,318 sites were robust hypermethylated in CIMP tumors *** of these CpG islands regulates 122 key genes in tumorgenesis and progress.A panel of 5 new markers was proposed for CIMP screening in 120 consecutive colon samples,13.3%(16/120)were methylated in all 5 markers and 87.5%(14/16)were *** the markers described by Weisenberger et al.,22.5%(27/120)were methylated in all 5 markers and only 51.8%(14/27)were MSI *** are a subset of colorectal cancer has unique features in DNA *** genes only hypermethylated in CIMP tumors shed lights on exploration the mechanism of CIMP tumorgenesis and provide new targets for cancer *** new panel of markers facilitates CIMP screening in sporadic colorectal cancers.

关键词： colorectal cancer CpG island methylator phenotype MBD-isolated genome sequencing DNA methylome

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Hepatitis C-induced upregulation of miR-155promotes hepatocarcinogenesis by activating Wnt signaling

Hepatitis C-induced upregulation of miR-155promotes hepatoca...

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中华医学会2012年医学遗传学年会暨全国第十一次医学遗传学学术会议

作者：章意亮孙树汉第二军医大学基础医学部医学遗传学教研室上海200433

Hepatitis C virus(HCV)infection induces chronic hepatic inflammation,which usually favors the initiation and progression of *** is also increasing clearly that microRNA-155 (miR-155)plays an important role in regulating both inflammation and ***,little is known about whether and how miR-155 provides the link between inflammation and *** we found that miR-155 levels were markedly increased after HCV infection and in hepatitis ***-155 expression was transcribed by NF-κB,and p300/CBP increased NF-κB-dependent miR-155 *** of miR-155 significantly inhibited hepatocytes apoptosis and promoted cells growth,whereas miR-155 inhibition induced G0/G1 *** miR-155 resulted in nuclear accumulation of β-catenin and a concomitant increase in cyclin D1,c-myc and ***-of-function and loss-of-function studies demonstrated that miR-155 promoted hepatocytes proliferation and tumorigenesis by increasing Wnt signaling in vitro and in vivo,and DKK1(Wnt pathway inhibitor)overexpression inhibited the biological role of miR-155 in ***,adenomatous polyposis coli(APC),which negatively regulates Wnt signaling,was identified as the direct and functional target of ***:Hepatitis C-induced upregulation of miR-155 promotes hepatocytes proliferation and tumorigenesis by activating Wnt *** present study provides a better understanding of the relationship between inflammation and tumor,and thus may be helpful in developing effective diagnosis and treatment strategies against HCV-HCC.

关键词： miR-155 wnt HCV HCC

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DNA methylation activates CTCF-mediated silencing of GAD1in colon and liver cancer by perturbing chromatin-loop formation

DNA methylation activates CTCF-mediated silencing of GAD1in ...

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中华医学会2012年医学遗传学年会暨全国第十一次医学遗传学学术会议

作者：颜宏利唐冠楠章意亮王玉招孙树汉第二军医大学基础医学部医学遗传学教研室上海200433

It is widely accepted that aberrant DNA methylation at promoter regions commonly occurs in cancer cells and has been implicated in the epigenetic silencing of tumor suppressor *** we demonstrate that the human GAD1 promoter were hypermethylated both in cancer cells and in clinical samples that expressed high amounts of *** of DNA methyltransferases decreased GAD1 mRNA levels,suggesting that hypermethylation plays a positive role in GAD1 *** further mapped the key region regulate GAD1 expression to an intragenic CpG island and found that the chromatin loop between 5-UTR and the intron 3 mediated by transcription factor CTCF was abolished by DNA *** findings indicated that DNA methylation could activate GAD1 expression by preventing CTCF-mediated *** DNA methylation at gene promoter often linked to silence tumor suppressor genes in cancer,recent genome-wide methylation studies have markedly changed the conception of DNA methylation negatively regulate gene expression in the mammalian *** demonstrated here that hypermethylation prevents CTCF-mediated silencing of GAD 1 by perturbing chromatin-loop *** is the first time,to my knowledge,to elucidate the mechanism underlying GAD1 transcription activation in *** results also provide a graphic example of aberrant DNA methylation in cancer should not always be considered as a "silencing marker"for tumor suppressor genes,as it can also serve to promote expression of oncogenes.

关键词： DNA methylation glutamate decarboxylase 1 CTCF oncogene

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UBE2C在斑马鱼胚胎发育过程中的功能研究

UBE2C在斑马鱼胚胎发育过程中的功能研究

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2014全球华人遗传学大会全国第十三次医学遗传学学术会议

目的:本课题旨在观察ube2c在斑马鱼胚胎发育过程中的时空表达规律,并对其功能进行研究。方法:选择2hpf(受精后2h)、4hpf、8hpf、12 hpf、24 hpf、48 hpf、72 hpf、7dpf(受精后7d)的斑马鱼胚胎,进行Real-Time RCR、western blot对ube2c... 详细信息

目的:本课题旨在观察ube2c在斑马鱼胚胎发育过程中的时空表达规律,并对其功能进行研究。方法:选择2hpf(受精后2h)、4hpf、8hpf、12 hpf、24 hpf、48 hpf、72 hpf、7dpf(受精后7d)的斑马鱼胚胎,进行Real-Time RCR、western blot对ube2c在不同时间段的表达检测;对各时期胚胎进行整胚原位杂交,观察ube2c在斑马鱼不同时期胚胎中时间

关键词：斑马鱼胚胎发育过程 UBE2C 整胚原位杂交胚胎发育功能研究

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LncRNA-LALR accelerates hepatocyte proliferation and cell cycle progression in liver regeneration by Wnt/β-Catenin signaling

LncRNA-LALR accelerates hepatocyte proliferation and cell cy...

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中华医学会2012年医学遗传学年会暨全国第十一次医学遗传学学术会议

作者：徐丹杨富毕海姗张铃周传传袁继行刘峰王芳孙树汉第二军医大学基础医学部医学遗传学教研室上海200433

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Epigenetic Activation of MiR-200Family Contributes to H19mediated Metastasis Suppression in Hepatocellular Carcinoma

Epigenetic Activation of MiR-200Family Contributes to H19med...

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中华医学会2012年医学遗传学年会暨全国第十一次医学遗传学学术会议

作者：张铃杨富孙树汉第二军医大学基础医学部医学遗传学教研室上海200433

Recently,long non-coding RNA is thought to be contained in human genome as important regulatory transcripts in which we can identify far more previously *** serve as scaffolds associating with a protein and genome *** our recent study,we identified non-overlapping signatures of a small number of lncRNAs that are aberrantly expressed in human HBV-related HCC compared to paired pertitumoral tissues and among which lncRNA H19 was found to speculate a potential role in HCC *** from past studies has shown a strong association between H19 and carcinogenesis in several types of cancer including *** expression of H19 usually changes from monoallelic to biallelic in HCC through aberrant DNA methylation.

关键词： epigenetics histone acetylation hepatocellular carcinoma aggressiveness peritumoral tissues epithelial-to-mesenchymal transition

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