20 results on '"Qiu GH"'
Search Results
2. Preparation and Properties of Broadband Terahertz Absorbing Coatings
- Author
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Qiu, GH, primary, Wang, W, additional, Han, JL, additional, Zhang, RR, additional, Han, L, additional, Wang, YK, additional, and Yu, MX, additional
- Published
- 2023
- Full Text
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3. Design, Preparation and Characterization of Mid-infrared Low-emissivity Film
- Author
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Han, JL, primary, Qiu, GH, additional, Zhang, RR, additional, Wang, W, additional, Liu, YF, additional, and Yu, MX, additional
- Published
- 2023
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4. PHA665752 inhibits the HGF-stimulated migration and invasion of cells by blocking PI3K/AKT pathway in uveal melanoma
- Author
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Qiu Gh, Xiuping Chen, Zhenning Wang, He C, Liu L, Zheng D, and Ma N
- Subjects
Uveal Neoplasms ,0301 basic medicine ,Cancer Research ,Indoles ,Mice, Nude ,Motility ,Biology ,Metastasis ,Mice ,Phosphatidylinositol 3-Kinases ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Cell Movement ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Neoplasm Invasiveness ,LY294002 ,Sulfones ,Melanoma ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Hepatocyte Growth Factor ,medicine.disease ,Xenograft Model Antitumor Assays ,Cell biology ,030104 developmental biology ,Oncology ,chemistry ,Cell culture ,030220 oncology & carcinogenesis ,Cancer research ,Phosphorylation ,Proto-Oncogene Proteins c-akt ,Signal Transduction - Abstract
HGF/c-MET is frequently associated with tumor metastasis in many cancers, including uveal melanoma (UM). PHA665752, a selective c-MET inhibitor, exhibits anticancer activity through inhibiting cell motility in some cancers. In this study, we investigated the effects of PHA665752 on UM cell lines M17 and SP6.5. Our data show that HGF stimulated the motility of UM cells, and induced the activation of both c-MET and PI3K/AKT, but not ERK1/2. Moreover, consistent with the amount of c-MET within the nucleus, PHA665752 significantly inhibited HGF-promoted cell motility and suppressed the phosphorylation of c-MET and PI3K/AKT, but not ERK1/2 induced by HGF. Additionally, the effects of PHA665752 on both the inhibition of HGF-induced cell motility and the suppression of active AKT are similar to those of PI3K inhibitor LY294002. In xenograft models, PHA665752 significantly inhibited tumor growth in nude mice and similarly suppressed the phosphorylation of c-MET and PI3K/AKT. Our current findings, combined with previous results, demonstrate that PHA665752 inhibits HGF-induced motility via the inhibition of PI3K/AKT. This study suggests that targeting HGF/c-MET could be a promising therapeutic strategy for UM by preventing cell motility.
- Published
- 2017
5. Recurrent pleural effusion as a rare manifestation after prolonged PD1 inhibitor (camrelizumab)-based immunotherapy: A case report.
- Author
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Xie XH, Shen PX, Wu JH, Qiu GH, Lin XQ, Xie ZH, Qin YY, Zheng B, Liu M, and Zhou CZ
- Subjects
- Humans, Immune Checkpoint Inhibitors adverse effects, Immunotherapy adverse effects, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms drug therapy, Pleural Effusion chemically induced, Pleural Effusion drug therapy
- Abstract
Immune-related adverse events (irAEs) pose a significant challenge for the widespread adoption of immuno-oncology therapies, but their symptoms can vary widely. In particular, the relationship between irAEs and pleural effusion (PE) in patients with advanced non-small cell lung cancer (NSCLC) remains unclear. In this report, we present the case of an advanced NSCLC patient who developed persistent PE despite receiving camrelizumab (an anti-programmed death receptor 1 [PD-1] antibody) and chemotherapy as first-line treatment. While the patient's tumor biomarkers decreased after multiple cycles of treatment, the PE persisted despite negative findings on cytology and pleural biopsy. Additionally, the use of anti-angiogenic drugs failed to alleviate the PE. Screening for rheumatic connective tissue markers and tuberculosis yielded negative results, but intrathoracic dexamethasone injections in two doses resulted in a significant reduction of the PE. This case suggests that PE may represent a rare type of irAE that should be monitored for during prolonged immuno-oncology therapy.
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- 2023
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6. Polymer negative curvature ring-core fiber for OAM modes guidance.
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Zhu ZH, Yan DX, Li XJ, Zhang L, Qiu GH, and Li JN
- Abstract
In this paper, a novel, to the best of our knowledge, polymer-based negative curvature ring-core fiber (NC-RCF) is proposed and investigated. The hollow-core NC-RCF is composed of TOPAS as background material. The inner and outer negative curvature structure layers are connected to the annular area, and the orbital angular momentum (OAM) modes can propagate in the annular core. In the frequency region of 1.0-1.5 THz, the designed NC-RCF can stably transmit 82 OAM modes. Investigation results indicate that the effective refractive index differences between the corresponding HE and EH modes are above 10
-4 . The confinement losses of EH or HE modes are smaller than 10-8 d B / m , and the dispersion variations are lower than 0.31 ps/THz/cm. Effective mode areas are larger than 5.14 m m2 . Additionally, the highest mode purity of all vector modes is 99.78%. In addition, modal birefringence, also known as the walk-off length, has also been discussed. All these operation performances indicate that the designed NC-RCF make contributions to the optical communication systems.- Published
- 2022
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7. A New Belief-Based Bidirectional Transfer Classification Method.
- Author
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Liu ZG, Qiu GH, Wang SY, Li TC, and Pan Q
- Subjects
- Learning, Machine Learning
- Abstract
In pattern classification, we may have a few labeled data points in the target domain, but a number of labeled samples are available in another related domain (called the source domain). Transfer learning can solve such classification problems via the knowledge transfer from source to target domains. The source and target domains can be represented by heterogeneous features. There may exist uncertainty in domain transformation, and such uncertainty is not good for classification. The effective management of uncertainty is important for improving classification accuracy. So, a new belief-based bidirectional transfer classification (BDTC) method is proposed. In BDTC, the intraclass transformation matrix is estimated at first for mapping the patterns from source to target domains, and this matrix can be learned using the labeled patterns of the same class represented by heterogeneous domains (features). The labeled patterns in the source domain are transferred to the target domain by the corresponding transformation matrix. Then, we learn a classifier using all the labeled patterns in the target domain to classify the objects. In order to take full advantage of the complementary knowledge of different domains, we transfer the query patterns from target to source domains using the K-NN technique and do the classification task in the source domain. Thus, two pieces of classification results can be obtained for each query pattern in the source and target domains, but the classification results may have different reliabilities/weights. A weighted combination rule is developed to combine the two classification results based on the belief functions theory, which is an expert at dealing with uncertain information. We can efficiently reduce the uncertainty of transfer classification via the combination strategy. Experiments on some domain adaptation benchmarks show that our method can effectively improve classification accuracy compared with other related methods.
- Published
- 2022
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8. Vanadium dioxide-assisted switchable multifunctional metamaterial structure.
- Author
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Qiu Y, Yan DX, Feng QY, Li XJ, Zhang L, Qiu GH, and Li JN
- Abstract
A multifunctional design based on vanadium dioxide (VO
2 ) metamaterial structure is proposed. Broadband absorption, linear-to-linear (LTL) polarization conversion, linear-to-circular (LTC) polarization conversion, and total reflection can be achieved based on the insulator-to-metal transition (IMT) of VO2 . When the VO2 is in the metallic state, the multifunctional structure can be used as a broadband absorber. The results show that the absorption rate exceeds 90% in the frequency band of 2.17 - 4.94 THz, and the bandwidth ratio is 77.8%. When VO2 is in the insulator state, for the incident terahertz waves with a polarization angle of 45°, the structure works as a polarization converter. In this case, LTC polarization conversion can be obtained in the frequency band of 0.1 - 3.5 THz, and LTL polarization conversion also can be obtained in the frequency band of 3.5 - 6 THz, especially in the 3.755 - 4.856 THz band that the polarization conversion rate is over 90%. For the incident terahertz waves with a polarization angle of 0°, the metamaterial structure can be used as a total reflector. Additionally, impacts of geometrical parameters, incidence angle and polarization angle on the operating characteristics have also been investigated. The designed switchable multifunctional metasurfaces are promising for a wide range of applications in advanced terahertz research and smart applications.- Published
- 2022
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9. Rare location and drainage pattern of right pulmonary veins and aberrant right upper lobe bronchial branch: A case report.
- Author
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Wang FQ, Zhang R, Zhang HL, Mo YH, Zheng Y, Qiu GH, and Wang Y
- Abstract
Background: Complex aberration in lung is rare, which may increase risk of vascular injury and cause ligation of wrong pulmonary vein or bronchus by mistake during lung surgery, and result in sever complication like pulmonary congestion or atelectasis., Case Summary: A 44-year-old female was admitted for a ground glass nodule (24 mm in diameter) in her right upper lobe. Video-assisted thoracoscopic (VATS) right upper lobectomy with lymph nodes dissection was performed. During operation, we simultaneously identified extremely rare aberrations of right preeparterial bronchus, right upper lobe vein behind pulmonary artery and right middle lobe vein drained into left atrium in this patient. The patient was well recovered and discharged at the postoperative-day 4., Conclusion: Preoperatively, three-dimensional reconstruction can help to identify inconspicuous variation of pulmonary vessels and bronchus effectively. During lung surgery, if anatomic aberration is suspected, careful dissection of vessels and bronchus will help to confirm whether there is an aberration or not., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)
- Published
- 2021
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10. Effects of miRNA-140 on the Growth and Clinical Prognosis of SMMC-7721 Hepatocellular Carcinoma Cell Line.
- Author
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Kong CQ, Chen XC, Qiu GH, Liang JC, Wang D, Liu XY, Liu JJ, Han YQ, and Fan XH
- Subjects
- Cell Line, Tumor, Disease-Free Survival, Humans, Neoplasm Invasiveness, Survival Rate, Carcinoma, Hepatocellular genetics, Carcinoma, Hepatocellular metabolism, Carcinoma, Hepatocellular mortality, Cell Movement, Cell Proliferation, Liver Neoplasms genetics, Liver Neoplasms metabolism, Liver Neoplasms pathology, MicroRNAs biosynthesis, MicroRNAs genetics, RNA, Neoplasm biosynthesis, RNA, Neoplasm genetics
- Abstract
Background: A growing number of studies have suggested that microRNAs exert an essential role in the development and occurrence of multiple tumours and act as crucial regulators in various biological processes. However, the expression and function of miRNA-140 in hepatocellular carcinoma (HCC) cells are not yet adequately identified and manifested., Methods: The expression of miRNA-140 was determined in HCC tissues and adjacent nontumour tissues by quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan-Meier survival analysis and Cox regression analysis were performed to explore the correlation between miRNA-140 expression level and the survival rate of patients with HCC. Additionally, overexpression experiments were conducted to investigate the biological role of miRNA-140 in HCC cells. Bioinformatics was used to predict the related target genes and pathways of miRNA-140., Results: QRT-PCR results signified that the expression level of miRNA-140 in HCC was lower than that of adjacent normal tissues ( P < 0.0001). Compared with the control group, the SMMC-7721 HCC cells in the miRNA-140 mimic group had a decrease in proliferation, migration, and invasion ( P < 0.05), whereas those in the miRNA-140 inhibitor group had an increase in proliferation, migration, and invasion ( P < 0.05). Cell cycle arrest occurred in the G0/1 phase. Prognosis analysis showed that the expression level of miRNA-140 was not related to the prognosis of HCC. Furthermore, the Kaplan-Meier test revealed that patients with lower miRNA-140 expression levels in liver cancer tissue had significantly shorter disease-free survival (DFS, P = 0.004) and overall survival (OS) times ( P = 0.010) after hepatectomy. Cox regression analysis further indicated that miRNA-140 was an independent risk factor that may affect the DFS ( P = 0.004) and OS times ( P = 0.014) of patients after hepatectomy. Our results suggested that miRNA-140 might be a crucial regulator involved in the HCC progression and is thus considered a potential prognostic biomarker and therapeutic target for HCC., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021 Cun-qing Kong et al.)
- Published
- 2021
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11. The pro-survival function of DLEC1 and its protection of cancer cells against 5-FU-induced apoptosis through up-regulation of BCL-XL.
- Author
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Qiu GH, Que W, Yan S, Zheng X, Xie X, Huang C, Yang X, and Hooi SC
- Abstract
The tumor suppressor DLEC1 has been shown to promote cell proliferation when AP-2α2 is down-regulated in HCT116 stable clones, suggesting its pro-survival nature. However, the pro-survival function of DLEC1 has not been confirmed in other cells and its underlying mechanisms remain elusive. Therefore, we knocked down DLEC1 in a panel of cell lines and found that DLEC1 depletion caused various extents of cell death through intrinsic pathway. DLEC1 overexpression promoted cell survival and reduced cell death in cancer cells after 5-FU treatment, while DLEC1 down-regulation sensitized cancer cells to 5-FU. Further studies demonstrated that DLEC1 attenuated the increase in cleaved PARP, caspase-3 and caspase-7, the activity of caspase-9 and the diffusion of cytosolic cytochrome c from mitochondria. Our data also showed that BCL-XL was up-regulated by DLEC1 in stable clones after 5-FU treatment. Altogether, these results indicated that DLEC1 protects cells against cell death induced by 5-FU through the attenuation of active proteins in caspase cascade and the up-regulation of BCL-XL. Therefore, DLEC1 can be a pro-survival protein under certain circumstances and a potential therapeutic target for increasing sensitivity of cancer cells to 5-FU.
- Published
- 2019
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12. The protective function of noncoding DNA in genome defense of eukaryotic male germ cells.
- Author
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Qiu GH, Huang C, Zheng X, and Yang X
- Subjects
- Animals, Cell Nucleus genetics, Cytosol metabolism, DNA Damage, Embryo, Mammalian, Gene Silencing, Genome, Humans, Male, RNA, Small Untranslated metabolism, Spermatozoa radiation effects, Telomere Homeostasis, DNA physiology, Spermatozoa metabolism
- Abstract
Peripheral and abundant noncoding DNA has been hypothesized to protect the genome and the central protein-coding sequences against DNA damage in somatic genome. In the cytosol, invading exogenous nucleic acids may first be deactivated by small RNAs encoded by noncoding DNA via mechanisms similar to the prokaryotic CRISPR-Cas system. In the nucleus, the radicals generated by radiation in the cytosol, radiation energy and invading exogenous nucleic acids are absorbed, blocked and/or reduced by peripheral heterochromatin, and damaged DNA in heterochromatin is removed and excluded from the nucleus to the cytoplasm through nuclear pore complexes. To further strengthen the hypothesis, this review summarizes the experimental evidence supporting the protective function of noncoding DNA in the genome of male germ cells. Based on these data, this review provides evidence supporting the protective role of noncoding DNA in the genome defense of sperm genome through similar mechanisms to those of the somatic genome.
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- 2018
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13. The eukaryotic genome is structurally and functionally more like a social insect colony than a book.
- Author
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Qiu GH, Yang X, Zheng X, and Huang C
- Subjects
- Animals, Cell Nucleus genetics, Evolution, Molecular, Humans, Open Reading Frames, Regulatory Sequences, Nucleic Acid genetics, Genome, Models, Genetic
- Abstract
Traditionally, the genome has been described as the 'book of life'. However, the metaphor of a book may not reflect the dynamic nature of the structure and function of the genome. In the eukaryotic genome, the number of centrally located protein-coding sequences is relatively constant across species, but the amount of noncoding DNA increases considerably with the increase of organismal evolutional complexity. Therefore, it has been hypothesized that the abundant peripheral noncoding DNA protects the genome and the central protein-coding sequences in the eukaryotic genome. Upon comparison with the habitation, sociality and defense mechanisms of a social insect colony, it is found that the genome is similar to a social insect colony in various aspects. A social insect colony may thus be a better metaphor than a book to describe the spatial organization and physical functions of the genome. The potential implications of the metaphor are also discussed.
- Published
- 2017
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14. Tumor Suppressor DLEC1 can Stimulate the Proliferation of Cancer Cells When AP-2ɑ2 is Down-Regulated in HCT116.
- Author
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Qiu GH, Xie X, Deng L, and Hooi SC
- Abstract
Background: The molecular mechanisms of tumor suppressor gene DLEC1 are largely unknown., Objectives: In this study, we established DLEC1 over-expression stable clones to study the cellular function of DLEC1 in the colorectal cancer cell line, HCT116., Materials and Methods: Stable clones with DLEC1 over-expression were first established by the transfection of DLEC1 expression construct pcDNA31DLEC1 in HCT116. On G418 selection, positive stable clones were screened for DLEC1 expression level by conventional reverse transcription-polymerase chain reaction (RT-PCR), and verified by real-time RT-PCR and Western blotting. Subsequently, these stable clones were subjected to colony formation and cell cycle analyses and identification of factors involved in G1 arrest. Lastly, three stable clones, DLEC1-7 (highest DLEC1 expression), DLEC1-3 (lowest expression) and pcDNA31 vector control, were employed to analyze cell proliferation and cell cycle after AP-2α2 knockdown by siRNAs., Results: The DLEC1 over-expression was found to reduce the number of colonies in colony formation and to induce G1 arrest in seven clones, and apoptosis in one clone in the cell cycle analysis. Furthermore, regardless of the different cell cycle defects in all eight stable clones, the expression level of transcriptional factor AP-2α2 was found to be elevated. More interestingly, we found that when AP-2α2 was knocked down, DLEC1 over-expression neither suppressed cancer cell growth nor induced G1 arrest, yet, instead promoted cell growth and decreased cells in the G1 fraction. This promotion of cell proliferation and release of G1 cells also seemed to be proportional to DLEC1 expression levels in DLEC1 stable clones., Conclusions: DLEC1 suppresses tumor cell growth the presence of AP-2α2 and stimulates cell proliferation in the down-regulation of AP-2α2 in DLEC1 over-expression stable clones of HTC116.
- Published
- 2015
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15. Distinctive pharmacological differences between liver cancer cell lines HepG2 and Hep3B.
- Author
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Qiu GH, Xie X, Xu F, Shi X, Wang Y, and Deng L
- Abstract
As cellular models for in vitro liver cancer and toxicity studies, HepG2 and Hep3B are the two most frequently used liver cancer cell lines. Because of their similarities they are often treated as the same in experimental studies. However, there are many differences that have been largely over-sighted or ignored between them. In this review, we summarize the differences between HepG2 and Hep3B cell lines that can be found in the literature based on PubMed search. We particularly focus on the differential gene expression, differential drug responses (chemosensitivity, cell cycle and growth inhibition, and gene induction), signaling pathways associated with these differences, as well as the factors in governing these differences between HepG2 and Hep3B cell lines. Based on our analyses of the available data, we suggest that neither HBx nor p53 may be the crucial factor to determine the differences between HepG2 and Hep3B cell lines although HBx regulates the expression of the majority of genes that are differentially expressed between HepG2 and Hep3B. Instead, the different maturation stages in cancer development of the original specimen between HepG2 and Hep3B may be responsible for the differences between them. This review provides insight into the molecular mechanisms underlying the differences between HepG2 and Hep3B and help investigators especially the beginners in the areas of liver cancer research and drug metabolism to fully understand, and thus better use and interpret the data from these two cell lines in their studies.
- Published
- 2015
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16. Recognition and suppression of transfected plasmids by protein ZNF511-PRAP1, a potential molecular barrier to transgene expression.
- Author
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Qiu GH, Leung CH, Yun T, Xie X, Laban M, and Hooi SC
- Subjects
- Carrier Proteins genetics, Cell Line, Tumor, Cyclin-Dependent Kinase Inhibitor p21 genetics, Genes, Reporter, Genetic Therapy methods, Genetic Vectors, Histone Deacetylase 2 genetics, Histone Deacetylase 2 metabolism, Humans, Hydroxamic Acids pharmacology, Plasmids antagonists & inhibitors, Plasmids metabolism, Pregnancy Proteins genetics, Promoter Regions, Genetic, RNA, Small Interfering genetics, Recombinant Proteins genetics, Recombinant Proteins metabolism, Transcription Factors drug effects, Transfection, Carrier Proteins metabolism, Gene Expression, Gene Transfer Techniques, Plasmids genetics, Pregnancy Proteins metabolism, Transcription Factors metabolism, Transgenes genetics
- Abstract
Nonviral vectors present considerable advantages over viral counterparts in gene transfer. However, the poor expression efficiency of the transfected genes poses a challenge for their use in gene therapy, primarily due to the inability of these vectors to overcome various barriers, including the biological barriers. Here, we report that ZNF511-PRAP1 may be involved in the recognition and inactivation of transfected plasmids. ZNF511-PRAP1 is induced by transfection of plasmid DNA and suppresses the transcription of transfected plasmids. It binds directly to the p21 promoter in transfected plasmids but not the endogenous counterpart. Similarly, ZNF511-PRAP1 suppresses the expression of the green fluorescent protein reporter gene on transiently transfected plasmids but not an integrated red fluorescence reporter gene with the same cytomegalovirus (CMV) promoter. Therefore, ZNF511-PRAP1 is able to differentiate between exogenous/nonintegrated and endogenous/integrated DNA. The suppression by ZNF511-PRAP1 is independent of DNA methylation and can be abolished by trichostatin A (TSA) treatment and knockdown of HDAC2 and/or ZNF511-PRAP1. Furthermore, ZNF511-PRAP1 interacts directly with HDAC2. Our results revealed that transfected plasmids are recognized by ZNF511-PRAP1 and suppressed by a repressor complex comprising ZNF511-PRAP1 and HDAC2 and suggest that ZNF511-PRAP1 could play a role as a potential molecular barrier in nonviral transgene expression.
- Published
- 2011
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17. DLEC1 is a functional 3p22.3 tumour suppressor silenced by promoter CpG methylation in colon and gastric cancers.
- Author
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Ying J, Poon FF, Yu J, Geng H, Wong AH, Qiu GH, Goh HK, Rha SY, Tian L, Chan AT, Sung JJ, and Tao Q
- Subjects
- Cell Line, Tumor, Chromosomes, Human, Pair 3 genetics, Chromosomes, Human, Pair 3 metabolism, Colon metabolism, Colonic Neoplasms metabolism, Female, Gene Silencing, Humans, Male, Stomach Neoplasms metabolism, Tumor Suppressor Proteins genetics, Colonic Neoplasms genetics, CpG Islands, DNA Methylation, Gene Expression Regulation, Neoplastic, Promoter Regions, Genetic, Stomach Neoplasms genetics, Tumor Suppressor Proteins metabolism
- Abstract
Promoter CpG methylation of tumour suppressor genes (TSGs) is an epigenetic biomarker for TSG identification and molecular diagnosis. We screened genome wide for novel methylated genes through methylation subtraction of a genetic demethylation model of colon cancer (double knockout of DNMT1 and DNMT3B in HCT116) and identified DLEC1 (Deleted in lung and oesophageal cancer 1), a major 3p22.3 TSG, as one of the methylated targets. We further found that DLEC1 was downregulated or silenced in most colorectal and gastric cell lines due to promoter methylation, whereas broadly expressed in normal tissues including colon and stomach, and unmethylated in expressing cell lines and immortalised normal colon epithelial cells. DLEC1 expression was reactivated through pharmacologic or genetic demethylation, indicating a DNMT1/DNMT3B-mediated methylation silencing. Aberrant methylation was further detected in primary colorectal (10 out of 34, 29%) and gastric tumours (30 out of 89, 34%), but seldom in paired normal colon (0 out of 17) and gastric (1 out of 20, 5%) samples. No correlation between DLEC1 methylation and clinical parameters of gastric cancers was found. Ectopic expression of DLEC1 in silenced HCT116 and MKN45 cells strongly inhibited their clonogenicity. Thus, DLEC1 is a functional tumour suppressor, being frequently silenced by epigenetic mechanism in gastrointestinal tumours.
- Published
- 2009
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18. The candidate tumor suppressor gene BLU, located at the commonly deleted region 3p21.3, is an E2F-regulated, stress-responsive gene and inactivated by both epigenetic and genetic mechanisms in nasopharyngeal carcinoma.
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Qiu GH, Tan LK, Loh KS, Lim CY, Srivastava G, Tsai ST, Tsao SW, and Tao Q
- Subjects
- Alleles, Animals, Azacitidine pharmacology, Base Sequence, Carcinoma pathology, Cell Line, Cell Line, Tumor, Cell Transformation, Viral, CpG Islands, DNA Methylation, Decitabine, Enzyme Inhibitors pharmacology, Gene Deletion, Gene Expression Regulation, Neoplastic, Gene Silencing, Genes, Tumor Suppressor, Humans, Mice, Mice, Nude, Molecular Sequence Data, Nasopharyngeal Neoplasms pathology, Promoter Regions, Genetic, Protein Binding, Azacitidine analogs & derivatives, Carcinoma genetics, Chromosomes, Human, Pair 3, Epigenesis, Genetic, Nasopharyngeal Neoplasms genetics, Stress, Physiological genetics, Tumor Suppressor Proteins genetics
- Abstract
Loss of heterozygosity at 3p21 is common in various cancers including nasopharyngeal carcinoma (NPC). BLU is one of the candidate tumor suppressor genes (TSGs) in this region. Ectopic expression of BLU results in the inhibition of colony formation of cancer cells, suggesting that BLU is a tumor suppressor. We have identified a functional BLU promoter and found that it can be activated by environmental stresses such as heat shock, and is regulated by E2F. The promoter and first exon are located within a CpG island. BLU is highly expressed in testis and normal upper respiratory tract tissues including nasopharynx. However, in all seven NPC cell lines examined, BLU expression was downregulated and inversely correlated with promoter hypermethylation. Biallelic epigenetic inactivation of BLU was also observed in three cell lines. Hypermethylation was further detected in 19/29 (66%) of primary NPC tumors, but not in normal nasopharyngeal tissues. Treatment of NPC cell lines with 5-aza-2'-deoxycytidine activated BLU expression along with promoter demethylation. Although hypermethylation of RASSF1A, another TSG located immediately downstream of BLU, was detected in 20/27 (74%) of NPC tumors, no correlation between the hypermethylation of these two TSGs was observed (P=0.6334). In addition to methylation, homozygous deletion of BLU was found in 7/29 (24%) of tumors. Therefore, BLU is a stress-responsive gene, being disrupted in 83% (24/29) of NPC tumors by either epigenetic or genetic mechanisms. Our data are consistent with the interpretation that BLU is a TSG for NPC.
- Published
- 2004
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19. Frequent epigenetic inactivation of the RASSF1A tumor suppressor gene in Hodgkin's lymphoma.
- Author
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Murray PG, Qiu GH, Fu L, Waites ER, Srivastava G, Heys D, Agathanggelou A, Latif F, Grundy RG, Mann JR, Starczynski J, Crocker J, Parkes SE, Ambinder RF, Young LS, and Tao Q
- Subjects
- Apoptosis genetics, Child, DNA Methylation, Gene Expression Regulation, Neoplastic genetics, Humans, Promoter Regions, Genetic, Tumor Cells, Cultured, Tumor Suppressor Proteins genetics, Gene Silencing, Genes, Tumor Suppressor, Hodgkin Disease genetics
- Abstract
Epigenetic inactivation of RASSF1A, a putative tumor suppressor with proapoptotic activity, is frequently observed in a number of solid tumors, including a variety of epithelial cancers, but has not been described in hematopoietic tumors. We have analysed the expression and methylation status of RASSF1A in Hodgkin's lymphoma (HL)-derived cell lines, primary HL tumors and serum samples from HL patients. RASSF1A transcription was detectable in only 2/6 HL cell lines. Methylation-specific PCR and bisulfite genomic sequencing revealed that the RASSF1A promoter was hypermethylated in all four RASSF1A-nonexpressing cell lines. 5-aza-2'-deoxycytidine treatment resulted in demethylation of the promoter and RASSF1A expression in these lines. Hypermethylation of RASSF1A was also detected in 34/52 (65%) primary HL tumors and in 2/22 serum samples from these patients. Microdissection of Hodgkin/Reed-Sternberg (HRS) cells from several of these cases confirmed that the RASSF1A hypermethylation we detected in the analysis of whole tumor originated from the tumor cell population. Although hypermethylation of RASSF1A was detected in 5/6 non-Hodgkin's lymphoma (NHL)-derived cell lines, only rare primary NHL (1/10 of Burkitt's lymphoma, 1/12 of post-transplant lymphoma, 1/12 diffuse large B-cell lymphoma, 0/27 of nasal lymphoma, 0/8 follicular center cell lymphoma, 0/4 mantle cell lymphoma, 0/4 anaplastic large cell (Ki-1+) lymphoma, 0/2 MALT lymphoma) showed hypermethylation of the promoter. No methylation was detected in any of the 14 normal PBMC. These results point to an important role for epigenetic silencing of RASSF1A in the pathogenesis of HL. Inactivation of RASSF1A could be one mechanism by which HRS cells escape the apoptosis that should occur following nonproductive immunoglobulin gene rearrangements.
- Published
- 2004
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20. Defective de novo methylation of viral and cellular DNA sequences in ICF syndrome cells.
- Author
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Tao Q, Huang H, Geiman TM, Lim CY, Fu L, Qiu GH, and Robertson KD
- Subjects
- Abnormalities, Multiple enzymology, Abnormalities, Multiple genetics, Chromosomes, Human, Pair 1, Female, Humans, Immunologic Deficiency Syndromes enzymology, Male, Mutation, Syndrome, DNA Methyltransferase 3B, Chromosome Aberrations, DNA metabolism, DNA (Cytosine-5-)-Methyltransferases genetics, DNA Methylation, Face abnormalities, Immunologic Deficiency Syndromes genetics
- Abstract
ICF syndrome (immunodeficiency, centromere instability and facial anomalies) is a recessive human genetic disorder resulting from mutations in the DNA methyltransferase 3B (DNMT3B) gene. Patients with this disease exhibit numerous chromosomal abnormalities, including anomalous decondensation, pairing, separation and breakage, primarily involving the pericentromeric regions of chromosomes 1 and 16. Global levels of DNA methylation in ICF cells are only slightly reduced; however, certain repetitive sequences and genes on the inactive X chromosome of female ICF patients are significantly hypomethylated. In the present report, we analyze the molecular defect of de novo methylation in ICF cells in greater detail by making use of a model Epstein-Barr virus (EBV)-based system and three members of the unique cellular cancer-testis (C-T) gene family. Results with the EBV-based system indicate that de novo methylation of newly introduced viral sequences is defective in ICF syndrome. Limited de novo methylation capacity is retained in ICF cells, indicating that the mutations in DNMT3B are not complete loss-of-function mutations or that other DNMTs cooperate with DNMT3B. Analysis of three C-T genes (two on the X chromosome and one autosomal) revealed that loss of methylation from cellular gene sequences is heterogeneous, with both autosomal and X chromosome-based genes demonstrating sensitivity to mutations in DNMT3B. Aberrant hypomethylation at a number of loci examined correlated with altered gene expression levels. Lastly, no consistent changes in the protein levels of the DNA methyltransferases were noted when normal and ICF cell lines were compared.
- Published
- 2002
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