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Start Over Author "Yen RW" Topic colorectal neoplasms
3 results on '"Yen RW"'

1. Defining UHRF1 Domains that Support Maintenance of Human Colon Cancer DNA Methylation and Oncogenic Properties.

Author

Kong X, Chen J, Xie W, Brown SM, Cai Y, Wu K, Fan D, Nie Y, Yegnasubramanian S, Tiedemann RL, Tao Y, Chiu Yen RW, Topper MJ, Zahnow CA, Easwaran H, Rothbart SB, Xia L, and Baylin SB

Subjects
Animals, CCAAT-Enhancer-Binding Proteins genetics, Caco-2 Cells, Colorectal Neoplasms genetics, Colorectal Neoplasms metabolism, Colorectal Neoplasms pathology, CpG Islands, Female, Gene Expression Regulation, Neoplastic, HCT116 Cells, HT29 Cells, Histones genetics, Histones metabolism, Humans, Male, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred NOD, Mice, Nude, Mice, SCID, Mutation, Neoplasm Metastasis, PHD Zinc Fingers, Prognosis, Time Factors, Ubiquitin-Protein Ligases genetics, CCAAT-Enhancer-Binding Proteins metabolism, Colorectal Neoplasms enzymology, DNA Methylation, Epigenesis, Genetic, Ubiquitin-Protein Ligases metabolism
Abstract

UHRF1 facilitates the establishment and maintenance of DNA methylation patterns in mammalian cells. The establishment domains are defined, including E3 ligase function, but the maintenance domains are poorly characterized. Here, we demonstrate that UHRF1 histone- and hemimethylated DNA binding functions, but not E3 ligase activity, maintain cancer-specific DNA methylation in human colorectal cancer (CRC) cells. Disrupting either chromatin reader activity reverses DNA hypermethylation, reactivates epigenetically silenced tumor suppressor genes (TSGs), and reduces CRC oncogenic properties. Moreover, an inverse correlation between high UHRF1 and low TSG expression tracks with CRC progression and reduced patient survival. Defining critical UHRF1 domain functions and its relationship with CRC prognosis suggests directions for, and value of, targeting this protein to develop therapeutic DNA demethylating agents., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Published
2019
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2. CHD4 Has Oncogenic Functions in Initiating and Maintaining Epigenetic Suppression of Multiple Tumor Suppressor Genes.

Author

Xia L, Huang W, Bellani M, Seidman MM, Wu K, Fan D, Nie Y, Cai Y, Zhang YW, Yu LR, Li H, Zahnow CA, Xie W, Chiu Yen RW, Rassool FV, and Baylin SB

Subjects
8-Hydroxy-2'-Deoxyguanosine, Animals, Autoantigens metabolism, Cell Movement, Cell Proliferation, Clustered Regularly Interspaced Short Palindromic Repeats, Colorectal Neoplasms enzymology, Colorectal Neoplasms pathology, Colorectal Neoplasms surgery, DNA (Cytosine-5-)-Methyltransferases genetics, DNA (Cytosine-5-)-Methyltransferases metabolism, DNA Damage, DNA Glycosylases genetics, DNA Glycosylases metabolism, Deoxyguanosine analogs & derivatives, Deoxyguanosine metabolism, Disease-Free Survival, Down-Regulation, Enhancer of Zeste Homolog 2 Protein genetics, Enhancer of Zeste Homolog 2 Protein metabolism, HCT116 Cells, Histocompatibility Antigens genetics, Histocompatibility Antigens metabolism, Histone-Lysine N-Methyltransferase genetics, Histone-Lysine N-Methyltransferase metabolism, Humans, Kaplan-Meier Estimate, Mi-2 Nucleosome Remodeling and Deacetylase Complex metabolism, Mice, Inbred BALB C, Mice, Nude, Neoplasm Metastasis, Oxidative Stress, Proportional Hazards Models, RNA Interference, Receptors for Activated C Kinase, Receptors, Cell Surface genetics, Receptors, Cell Surface metabolism, Time Factors, Transcription, Genetic, Transfection, Tumor Suppressor Proteins, Autoantigens genetics, Colorectal Neoplasms genetics, DNA Methylation, Epigenetic Repression, Gene Expression Regulation, Neoplastic, Gene Silencing, Genes, Tumor Suppressor, Mi-2 Nucleosome Remodeling and Deacetylase Complex genetics
Abstract

An oncogenic role for CHD4, a NuRD component, is defined for initiating and supporting tumor suppressor gene (TSG) silencing in human colorectal cancer. CHD4 recruits repressive chromatin proteins to sites of DNA damage repair, including DNA methyltransferases where it imposes de novo DNA methylation. At TSGs, CHD4 retention helps maintain DNA hypermethylation-associated transcriptional silencing. CHD4 is recruited by the excision repair protein OGG1 for oxidative damage to interact with the damage-induced base 8-hydroxydeoxyguanosine (8-OHdG), while ZMYND8 recruits it to double-strand breaks. CHD4 knockdown activates silenced TSGs, revealing their role for blunting colorectal cancer cell proliferation, invasion, and metastases. High CHD4 and 8-OHdG levels plus low expression of TSGs strongly correlates with early disease recurrence and decreased overall survival., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Published
2017
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3. CpG island hypermethylation is maintained in human colorectal cancer cells after RNAi-mediated depletion of DNMT1.

Author

Ting AH, Jair KW, Suzuki H, Yen RW, Baylin SB, and Schuebel KE

Subjects
Base Sequence, DNA (Cytosine-5-)-Methyltransferase 1, DNA (Cytosine-5-)-Methyltransferases genetics, DNA (Cytosine-5-)-Methyltransferases metabolism, DNA Methylation, Gene Silencing, Genes, Tumor Suppressor, HCT116 Cells, Humans, Promoter Regions, Genetic, RNA Interference, RNA, Neoplasm genetics, RNA, Small Interfering genetics, Colorectal Neoplasms enzymology, Colorectal Neoplasms genetics, CpG Islands, DNA (Cytosine-5-)-Methyltransferases antagonists & inhibitors
Abstract

The role of the primary mammalian DNA methyltransferase, DNMT1, in maintaining CpG island methylation in human colon cancer cells has recently been questioned. This controversy has arisen from discrepancies between genetic knockout and RNA interference-mediated knockdown studies. Here, we re-examined the RNA interference-based approach and found that hypermethylation of single-copy genes is maintained in cells transiently and stably depleted of DNMT1.

Published
2004
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