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| 1 | 肝内和肝外胆管癌肿瘤抑制基因启动子甲基化分析显示文摘目的 探讨胆管癌的表遗传学改变。方法 用甲基化特异PCR(MSP)法 ,检测了 12个候选肿瘤抑制基因 (APGE cad herin/CDH1,MGMT ,RASSF1A ,GSTP ,RAR β ,p14 ARF,p15 INK4b,p16INK4a,p73 ,hMLH1,DAPK)启动子在 72例胆管癌中的甲基化情况 ,其中肝内和肝外胆管癌各 3 6例 ,10例良性胆管上皮作为对照。结果 85 %的胆管癌至少有一个肿瘤抑制基因的甲基化 ,在胆管癌中 ,肿瘤抑制基因的甲基化顺序是 :RASSF1A(65 %) ,p15 INK4b(5 0 %) ,p16INK4a(5 0 %) ,APC(4 6%) ,E cadherin/CDH1(4 3 %) ,p14 ARF(3 8%) ,p73 (3 6%) ,MGMT(3 3 %) ,hMHL1(2 5 %) ,GSTP(14 %) ,RAR β(14 %)和DAPK(3 %)。虽然单个肿瘤抑制基因的甲基化可见于良性胆管上皮 ,但是多个肿瘤抑制基因的甲基化只见于胆管癌。约 70 %(5 0 /72 )的胆管癌有 3个或 3个以上的肿瘤抑制基因的甲基化 ,5 2 %(3 8/72 )有 4个或 4个以上肿瘤抑制基因的甲基化。多个肿瘤抑制基因的协同甲基化 ,和RASSF1A ,p15 INK4b,p16INK4a和 /或hMHL1密切相关。RASSF1A的甲基化在肝外胆管癌 (83 %)较肝内胆管癌更常见 (4 7%) (P =0 . 0 0 3 ) ,而GSTP更多见于肝内胆管癌(肝内 3 1%,肝外 6%,P =0 . 0 12 ) ,本研究提示肿瘤抑制基因启动子CpG岛的甲基化在胆管癌中是一? | YANG Bin Michael G.House GUO Mingzhou James G.Herman Douglas P.Clark | 2005 | 胃肠病学和肝病学杂志2005,14,1: | 46 |
| 2 | DNA methylation-mediated repression of miR-181a/135a/302c expression promotes the microsatellite-unstable colorectal cancer development and 5-FU resistance via targeting PLAG1显示文摘Micro sate Hite instability(MSI) defines a subtype of colorectal cancer(CRC) with typical clinicopathologic characteristics. CRCs with MSI(MSI CRCs) frequently acquire accelerated carcinogenesis and 5-FU resistance, and the exact underlying mechanism remains incompletely understood. Our previous study has identified the microRNA(miRNA) expression profile in MSI CRCs. In this study, three miRNAs(miR-181 a, miR-135 a and miR-302 c) were validated by qRT-PCR to be dramatically decreased in 67 CRC samples. Proliferation and apoptosis assays demonstrated that miR-181 a/135 a/302 c function as tumor suppressors via repressing PLAG1/IGF2 signaling. Moreover, we presented compelling evidence that restoration of miR-181 a/135 a/302 c expression promoted sensitivity of MSI CRC cells to 5-FU treatment. miR-181 a/135 a/302 c exerted their effect on chemoresistance through attenuating PLAG1 expression. Notably, the hypermethylation status of MSI CRC accounts for the decrements of miR-181 a/135 a/302 c. Our results contribute to a better understanding of the mechanism of chemo?resistance in MSI CRCs, and provide a clue for digging the bio markers and therapeutic targets for CRC patients. | Lu Shi Xiang Li Zhiqiang Wu Xiaolei Li Jing Nie Mingzhou Guo Qian Mei Weidong Han | 2018 | Journal of Genetics and Genomics2018,45,4: | 9 |
| 3 | Epigenetic changes in colorectal cancer显示文摘Epigenetic changes frequently occur in human colorectal cancer.Genomic global hypomethylation,gene promoter region hypermethylation,histone modifications,and alteration of miRNA patterns are major epigenetic changes in colorectal cancer.Loss of imprinting(LOI) is associated with colorectal neoplasia.Folate deficiency may cause colorectal carcinogenesis by inducing gene-specific hypermethylation and genomic global hypomethylation.HDAC inhibitors and demethylating agents have been approved by the FDA for myelodysplastic syndrome and leukemia treatment.Non-coding RNA is regarded as another kind of epigenetic marker in colorectal cancer.This review is mainly focused on DNA methylation,histone modification,and microRNA changes in colorectal cancer. | Yan Jia Mingzhou Guo | 2013 | Chinese Journal of Cancer2013,32,1: | 7 |
| 4 | Amplification of the miR-181c/d cluster is inversely correlated with PDCD4 expression in gastric cancer显示文摘miR-181c/d is dysregulated in gastric cancer(GC).We investigated the amplification and expression of miR-181c/d and its predicted target genes in GC.Amplification of miR-181c/d was quantified by genomic real-time PCR in GC and adjacent normal tissues,as well as the levels of mature miR-181c/d was performed by real-time PCR in the same tissues.The potential target genes of miR-181c/d were predicted using bioinformatics software.Expression of one potential target gene,PDCD4,was measured by semiquantitative RT-PCR,real-time PCR,and immunohistochemistry.Next,the relationship between miR181c/d expression and PDCD4 expression was analyzed.Results indicated that the amplification and expression of miR-181c/d were significantly higher in GC than in adjacent normal tissues(primary miR-181c/d,P\0.001;miR-181c,P=0.0344;miR-181d,P=0.0153),and there was a strong correlation between mature miR-181c/d and primary miR-181c/d.Thirty-two target genes were predicted,including PDCD4 which is a known tumor suppressor gene.Expression of PDCD4 was significantly down-regulated in GC as compared to adjacent normal tissues and was inversely correlated with miR-181c/d expression in GC(miR-181c and PDCD4:R=-0.496,P=0.008;miR-181d and PDCD4:R=-0.454,P=0.003).Therefore,miR-181c/d may play a pivotal role in the pathogenesis of GC by downregulating PDCD4 expression. | Yuanming Pan Rui Xing Juan An Jiantao Cui Wenmei Li Mingzhou Guo Youyong Lu | 2014 | Chinese Science Bulletin2014,59,19: | 6 |
| 5 | Differential expression analysis and regulatory network reconstruction for genes associated with muscle growth and adipose deposition in obese and lean pigs显示文摘During the growth and development of skeletal muscle cells and adipose cells, the regulatory mechanism of micro-effect polygenes determines porcine meat quality, carcass characteristics and other relative quantitative traits. Obese and lean type pig breeds show obvi- ous differences in muscle growth and adipose deposition; however, the molecular mechanism underlying this phenotypic variation remains unknown. We used pathway-focused oligo microarray studies to examine the expression changes of 140 genes associated with muscle growth and adipose deposition in longissimus dorsi muscle at six growth stages (birth, 1, 2, 3, 4 and 5 months) of Landrace (a leaner, Western breed) and Taihu pigs (a fatty, indigenous, Chinese breed). Variance analysis (ANOVA) revealed that differences in the expression of 18 genes in Landrace pigs and three genes in Taihu pigs were very significant (FDR-adjusted permutation, P < 0.01) and di?erences for 22 genes in Landrace pigs and seven genes in Taihu pigs were significant (FDR-adjusted permutation, P < 0.05) among six growth stages. Clustering analysis revealed a high level of signi?cance (FDR-adjusted, P < 0.01) for four gene expression patterns, in which genes that strongly up-regulated were mainly associated with the positive regulation of myofiber formation and fatty acid biogenesis and genes that strongly down-regulated were mainly associated with the inhibition of cell proliferation and positive regulation of fatty acid b-oxidation. Based on a dynamic Bayesian network (DBN) model, gene regulatory networks (GRNs) were reconstructed from time-series data for each pig breed. These two GRNs initially revealed the distinct differences in physiological and biochemical aspects of muscle growth and adipose deposition between the two pig breeds; from these results, some potential key genes could be identified. Quantitative real-time RT-PCR (QRT-PCR) was used to verify the microarray data for five modulated genes, and a good correlation between the two measures of expression was observed for both two pig breeds at different growth stages (r = 0.876 ± 0.095). These results highlight some possible candidate genes for porcine meat quality and carcass traits and provide some data on which gene(s) should be further studied for elucidating the molecular mechanism of muscle growth and fat deposition. | Mingzhou Li Xuewei Li Li Zhu Xiaokun Teng Huasheng Xiao Surong Shuai Lei Chen Qiang Li Yujiao Guo | 2008 | Progress in Natural Science:Materials International2008,18,4: | 5 |
| 6 | Clinical and pathological features of miR-10b and RHOC gene expression in hepatocellular carcinoma显示文摘Aberrant expression of microRNAs(miRNAs)was reported frequently in different human cancers.The major role of miRNA is targeting 30-UTR of coding gene and causing translational repression or mRNA degradation.miR-10b overexpression was reported to promote breast cancer metastasis by up-regulating RHOC expression.But its expression in hepatocellular carcinoma(HCC)remains unclear.Our study indicated that the expression of miR-10b was different in HCC and adjacent tissue samples,and reduced expression of miR-10b in HCC was related tovein invasion.High-level expression of RHOC was also related to vein invasion in HCC.But no correlation was found between miR-10b and RHOC expression.These results suggest that miR-10b and RHOC are independent predictors of HCC invasion and metastasis. | Jingli Du Yulan Wang Hanjiang Fu Xiaofei Zheng Minggui Lin Mingzhou Guo Lixin Wei | 2014 | Chinese Science Bulletin2014,59,19: | 4 |
| 7 | Generation and characterization of stable pig pregastrulation epiblast stem cell lines显示文摘Pig epiblast-derived pluripotent stem cells are considered to have great potential and broad prospects for human therapeutic model developme nt and livestock breeding.Despite on going attempts since the 1990s,no stably defined pig epiblast-derived stem cell line has bee n established.Here,guided by in sights from a large-scale sin gle-cell tran scriptome an alysis of pig embryos from embryonic day(E)0 to E14,specifically,the tracing of pluripotency changes during epiblast development,we developed an in vitro culture medium for establishing and maintaining stable pluripotent stem cell lines from pig E10 pregastrulation epiblasts(pgEpiSCs).Enabled by chemical inhibition of WNT-related signaling in combination with growth factors in the FGF/ERK,JAK/STAT3,and Activin/Nodal pathways,pgEpiSCs maintain their pluripotency transcriptome features,similar to those of E10 epiblast cells,and normal karyotypes after more than 240 passages and have the potential to differentiate into three germ layers.Strikingly,ultradeep in situ Hi-C analysis revealed functional impacts of chromatin 3D-spatial associations on the transcriptional regulation of pluripote ncy marker genes in pgEpiSCs.I n practice,we con firmed that pgEpiSCs readily tolerate at least three rounds of successive gene editi ng and gene rated cloned gen e-edited live piglets.Our findings deliver on the long-a nticipated promise of pig pluripote nt stem cells and open new avenues for biological research,animal husbandry,and regenerative biomedicine. | Minglei Zhi Jinying Zhang Qianzi Tang Dawei Yu Shuai Gao Dengfeng Gao Pengliang Liu Jianxiong Guo Tang Hai Jie Gao Suying Cao Zimo Zhao Chongyang Li Xiaogang Weng Mengnan He Tianzhi Chen Yingjie Wang Keren Long Deling Jiao Guanglei Li Jiaman Zhang Yan Liu Yu Lin Daxin Pang Qianqian Zhu Naixin Chen Jingjing Huang Xinze Chen Yixuan Yao Jingcang Yang Zicong Xie Xianya Huang Mengxin Liu Ran Zhang Qiuyan Li Yiliang Miao Jianhui Tian Xingxu Huang Hongsheng Ouyang Bofeng Liu Wei Xie Qi Zhou Zhonghua Liu Caihong Zheng Mingzhou Li Jianyong Han | 2022 | Cell Research2022,32,4: | 3 |
| 8 | Genome-wide analysis reveals selection for Chinese Rongchang pigs显示文摘Livestock have undergone domestication and consequently strong selective pressure on genes or genomic regions that control desirable traits. To identify selection signatures in the genome of Chinese Rongchang pigs, we generated a total of about 170 Gb of DNA sequence data with about 6.4-fold coverage for each of six female individuals. By combining these data with the publically available genome data of 10 Asian wild boars,we identified 449 protein-coding genes with selection signatures in Rongchang pigs, which are mainly involved in growth and hormone binding, nervous system development, and drug metabolism. The accelerated evolution of these genes may contribute to the dramatic phenotypic differences between Rongchang pigs and Chinese wild boars. This study illustrated how domestication and subsequent artificial selection have shaped patterns of genetic variation in Rongchang pigs and provides valuable genetic resources that can enhance the use of pigs in agricultural production and biomedical studies. | Lei CHEN Shilin TIAN Long JIN Zongyi GUO Dan ZHU Lan JING Tiandong CHE Qianzi TANG Siqing CHEN Liang ZHANG Tinghuan ZHANG Zuohua LIU Jinyong WANG Mingzhou LI | 2017 | Frontiers of Agricultural Science and Engineering2017,4,3: | 2 |
| 9 | Rice FLOURY ENDOSPERM 18 encodes a pentatricopeptide repeat protein required for 5′ processing of mitochondrial nad5 messenger RNA and endosperm development显示文摘Pentatricopeptide repeat(PPR) proteins, composing one of the largest protein families in plants,are involved in RNA binding and regulation of organelle RNA metabolism at the posttranscriptional level. Although several PPR proteins have been implicated in endosperm development in rice(Oryza sativa), the molecular functions of many PPRs remain obscure. Here, we identified a rice endosperm mutant named floury endosperm 18(flo18) with pleiotropic defects in both reproductive and vegetative development.Map-based cloning and complementation tests showed that FLO18 encodes a mitochondriontargeted P-type PPR protein with 15 PPR motifs.Mitochondrial function was disrupted in the flo18 mutant, as evidenced by decreased assembly of Complex I in the mitochondrial electron transport chain and altered mitochondrial morphology. Loss of FLO18 function resulted in defective 5′-end processing of mitochondrial nad5 transcripts encoding subunit 5 of nicotinamide adenine dinucleotide hydrogenase. These results suggested that FLO18 is involved in 5′-end processing of nad5 messenger RNA and plays an important role in mitochondrial function and endosperm development. | Mingzhou Yu Mingming Wu Yulong Ren Yihua Wang Jingfang Li Cailin Lei Yinglun Sun Xiuhao Bao Hongming Wu Hang Yang Tian Pan Yongfei Wang Ruonan Jing Mengyuan Yan Houda Zhang Lei Zhao Zhichao Zhao Xin Zhang Xiuping Guo Zhijun Cheng Bing Yang Ling Jiang Jianmin Wan | 2021 | Journal of Integrative Plant Biology2021,63,5: | 2 |
| 10 | Methylation‐induced loss of miR ‐484 in microsatellite‐unstable colorectal cancer promotes both viability and IL ‐8 production via CD137L显示文摘 | Qian Mei Geng Xue Xiang Li Zhiqiang Wu Xiaolei Li Hongli Yan Mingzhou Guo Shuhan Sun Weidong Han | 2015 | J. Pathol2015,,2: | 1 |
| 11 | Methylation of TFPI-2 is an early event of esophageal carcinogenesis显示文摘 | Yan Jia Yunsheng Yang Malcolm V Brock Baoping Cao Qimin Zhan Yazhuo Li Yuanzi Yu James G Herman Mingzhou Guo | 2012 | Epigenomics2012,,2: | 1 |
| 12 | MicroRNA-155 Is Involved in the Pathogenesis of Ulcerative Colitis by Targeting FOXO3a显示文摘 | Min Min Lihua Peng Yunsheng Yang Mingzhou Guo Weifeng Wang Gang Sun | 2014 | Inflammatory Bowel Diseases2014,,4: | 1 |
| 13 | Epigenetic regulation of the Wnt signaling inhibitor DACT2 in human hepatocellular carcinoma显示文摘 | Xiaomei Zhang Yunsheng Yang Xuefeng Liu James G. Herman Malcolm V. Brock Julien D.F. Licchesi Wen Yue Xuetao Pei Mingzhou Guo | 2013 | Epigenetics2013,,4: | 1 |
| 14 | High frequency of alternative splicing variants of the oncogene Focal Adhesion Kinase in neuroendocrine tumors of the pancreas and breast显示文摘The characteristic genetic abnormality of neuroendocrine neoplasms(NENs),a heterogeneous group of tumors found in various organs,remains to be identified.Here,based on the analysis of the splicing variants of an oncogene Focal Adhesion Kinase(FAK)in The Cancer Genome Atlas datasets that contain 9193 patients of 33 cancer subtypes,we found that Box 6/Box 7-containing FAK variants(FAK^(6/7))were observed in 7(87.5%)of 8 pancreatic neuroendocrine carcinomas and 20(11.76%)of 170 pancreatic ductal adenocarcinomas(PDACs).We tested FAK variants in 157 tumor samples collected from Chinese patients with pancreatic tumors,and found that FAK^(6/7)was positive in 34(75.6%)of 45 pancreatic NENs,19(47.5%)of 40 pancreatic solid pseudopapillary neoplasms,and 2(2.9%)of 69 PDACs.We further tested FAK splicing variants in breast neuroendocrine carcinoma(BrNECs),and found that FAK^(6/7)was positive in 14(93.3%)of 15 BrNECs but 0 in 23 non-NEC breast cancers.We explored the underlying mechanisms and found that a splicing factor serine/arginine repetitive matrix protein 4(SRRM4)was overexpressed in FAK^(6/7)-positive pancreatic tumors and breast tumors,which promoted the formation of FAK^(6/7)in cells.These results suggested that FAK^(6/7)could be a biomarker of NENs and represent a potential therapeutic target for these orphan diseases. | Dawei Xie Zheng Wang Beibei Sun Liwei Qu Musheng Zeng Lin Feng Mingzhou Guo Guizhen Wang Jihui Hao Guangbiao Zhou | 2023 | Frontiers of Medicine2023,17,5: | 0 |
| 15 | Targeted PERK inhibition with biomimetic nanoclusters confers preventative and interventional benefits to elastase-induced abdominal aortic aneurysms显示文摘Abdominal aortic aneurysm(AAA)is a progressive aortic dilatation,causing~80%mortality upon rupture.Currently,there is no approved drug therapy for AAA.Surgical repairs are invasive and risky and thus not recommended to patients with small AAAs which,however,account for~90%of the newly diagnosed cases.It is therefore a compelling unmet clinical need to discover effective non-invasive strategies to prevent or slow down AAA progression.We contend that the first AAA drug therapy will only arise through discoveries of both effective drug targets and innovative delivery methods.There is substantial evidence that degenerative smooth muscle cells(SMCs)orchestrate AAA pathogenesis and progression.In this study,we made an exciting finding that PERK,the endoplasmic reticulum(ER)stress Protein Kinase R-like ER Kinase,is a potent driver of SMC degeneration and hence a potential therapeutic target.Indeed,local knockdown of PERK in elastase-challenged aorta significantly attenuated AAA lesions in vivo.In parallel,we also conceived a biomimetic nanocluster(NC)design uniquely tailored to AAA-targeting drug delivery.This NC demonstrated excellent AAA homing via a platelet-derived biomembrane coating;and when loaded with a selective PERK inhibitor(PERKi,GSK2656157),the NC therapy conferred remarkable benefits in both preventing aneurysm development and halting the progression of pre-existing aneurysmal lesions in two distinct rodent models of AAA.In summary,our current study not only establishes a new intervention target for mitigating SMC degeneration and aneurysmal pathogenesis,but also provides a powerful tool to facilitate the development of effective drug therapy of AAA. | Nisakorn Yodsanit Takuro Shirasu Yitao Huang Li Yin Zain Husain Islam Alexander Christopher Gregg Alessandra Marie Riccio Runze Tang Eric William Kent Yuyuan Wang Ruosen Xie Yi Zhao Mingzhou Ye Jingcheng Zhu Yi Huang Nicholas Hoyt Mengxue Zhang John A.Hossack Morgan Salmon K.Craig Kent Lian-Wang Guo Shaoqin Gong Bowen Wang | 2023 | Bioactive Materials2023,,8: | 0 |