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中国老年学杂志 2012年第22期32卷 4925-4928页

作者：尚经轩虞璟隋建峰范蕊虞乐华重庆城市管理职业学院重庆医科大学临床学院第三军医大学基础医学部生理学教研室重庆医科大学附属第二医院康复理疗中心重庆400010

目的在同一豚鼠体上建立痕迹性和延迟性眨眼条件反射双任务模型,为研究认知过程中前额叶与其他脑区信息编码机制提供模型。方法以经典的眨眼条件反射为基础,采用1 kHz和3 kHz正弦波纯音分别配对压强为20 kPa的束状氧气流对豚鼠左侧眼角... 详细信息

目的在同一豚鼠体上建立痕迹性和延迟性眨眼条件反射双任务模型,为研究认知过程中前额叶与其他脑区信息编码机制提供模型。方法以经典的眨眼条件反射为基础,采用1 kHz和3 kHz正弦波纯音分别配对压强为20 kPa的束状氧气流对豚鼠左侧眼角膜进行刺激,利用肌肉张力换能器采集豚鼠眨眼活动,用眨眼条件反射行为特征传感器信号分析软件V2.2版分析眨眼数据。结果经过10 d的配对训练后,6只豚鼠均建立了痕迹性和延迟性眨眼条件反射双任务。实验发现,与痕迹性眨眼条件反射相比,豚鼠更容易建立延迟性眨眼条件反射。结论利用同一豚鼠首次成功建立了痕迹性和延迟性眨眼条件反射双行为模型。

关键词：痕迹性眨眼条件反射延迟性眨眼条件反射双任务模型

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The Histone Deacetylase4/Sp1/miR-200a Regulatory Network Contributes to Aberrant Histone Acetylation in Hepatocellular Carcinoma

The Histone Deacetylase4/Sp1/miR-200a Regulatory Network Con...

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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：袁继行杨富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

As an important epigenetic mechanism,histone acetylation modulates the transcription of many genes and plays important roles in hepatocellular carcinoma(HCC).Aberrations in histone acetylation have been observed in HCC,but the factors that contribute to the aberrations have not been fully ***(miRNAs),which are noncoding RNAs that regulate gene expression,are involved in important epigenetic *** this study,we determined that the miR-200a and the level ofhistone H3 acetylation at its promoter were reduced in human HCC tissues in comparison with adjacent noncancerous hepatic ***,our results suggested that the histone deacetylase 4(HDAC4)inhibited the expression of miR-200a and its promoter activity and reduced the histone H3 acetylation level at the mir-200a promoter through a Sp1-dependent ***,we observed that the miR-200a directly targeted the 3'untranslated region of the HDAC4 mRNA and repressed HDAC4's ***,the miR-200a ultimately induced its own transcription and increased the histone H3 acetylation level at its own *** targeting HDAC4,the miR-200a also induced the upregulation of total acetyl-histone H3 levels and increased the histone H3 acetylation level at the p21WAF/Cip1 ***,we determined that the miR-200a inhibited the proliferation and migration of HCC cells in vivo and in ***:Our findings suggest that the HDAC4/Sp1/miR-200a regulatory network induces the downregulation of the miR-200a and the upregulation of HDAC4 in *** a consequence,the downregulation of the miR-200a enhances the proliferation and migration of the HCC cells and induces aberrant histone acetylation in *** findings highlight a potential therapeutic approach in targeting the HDAC4/Sp1/miR-200a regulatory network for the treatment of HCC.

关键词： histone deacetylase 4 Sp1 miR-200a histone acetylation hepatocellular carcinoma

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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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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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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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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：黄金凤郭瀛军王坡赵晨曦唐冠楠王越刘音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

Liver cancer is the fifth most common cancer in the world and the third most common cause of cancer-related ***,50% to 55% of cases of primary liver cancer are attributable to persistent hepatitis B virus(HBV)*** the pathogenesis of liver cancer is not very clear at *** the in-depth understanding of cancer,it is recognized that epigenetic modifications play crucial roles in the initiation and development of human *** is as much an epigenetic disease as it is a genetic disease,which together lead to the malignant transformation of cells caused by the activation of oncogene and the inactivation of tumor suppressor genes.

关键词： epigenetics hepatocellular carcinoma hepatitis B virus X protein long non-coding RNA vimentin

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Evi-1is a critical regulator of the HBx-induced aberrant transcription of long non-coding RNAs

Evi-1is a critical regulator of the HBx-induced aberrant tra...

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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：郭瀛军王越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

The role of long non-coding RNAs(lncRNAs)in tumorigenesis is gradually being elucidated largely due to an increasing number of ***,the regulatory mechanism for lncRNA expression remains *** this study,we employed a systemic approach to analyze the key regulator of aberrantly expressed lncRNAs in HBV X protein(HBx)-transgenic mice,which is a well-proven mouse tumorigenesis model for hepatitis B virus-related hepatocellular *** a bioinformatics analysis of microarray data,ecotropic viral integration site 1(Evi-1)was identified as a key regulatory transcriptional factor contributing to the aberrant expression of lncRNAs in the livers of HBx-transgenic *** a consequence of the up-regulation of Evi-1,we also identified that an Evi-1-regulated lncRNA AK015487 contributed to hepatocyte proliferative activity and *** findings highlight a novel mechanism for hepatocellular carcinoma tumorigenesis through Evi-1 and its target *** addition,our study also provides a good model for investigation of the regulatory mechanism for lncRNA expression using a systemic approach.

关键词： hepatocarcinogenesis IncRNA Evi-1 HBx epigenetics

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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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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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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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