keyword
https://read.qxmd.com/read/38504782/the-effects-of-thymidylate-synthase-3-utr-genotype-on-methylation-of-tumor-specific-genes-promoter-in-22-colorectal-cancer-patients-from-southern-iran
#1
JOURNAL ARTICLE
Maryam Niknam, Fakhraddin Naghibalhossaini, Mozhdeh Zamani, Seyed Vahid Hosseini, Pooneh Mokarram
To investigate the effects of thymidylate synthase (TS) 3'UTR genotype on promotor methylation of tumor-related genes in 22 patients with sporadic colorectal cancer (CRC) from southern Iran. We evaluated the correlations of TS 3'UTR genotype with promoter methylation of hTERT, hMLH1, MSH2, MMP2, CDH1, p14, p16, and p21 genes in CRC patients. The polymorphism of TS 3'UTR was evaluated through mutagenically specific PCR. The genes promoter methylation was determined using methylation-specific PCR. For 10 patients, the gene expression profile of epigenetic regulating enzymes, histone deacetylases (HDACs) and DNA methyltransferases (DNMTs), was also examined in both tumor and normal adjacent tissues by quantitative real time PCR...
2024: Molecular Biology Research Communications
https://read.qxmd.com/read/38499720/dnmt3a1-regulates-hippocampus-dependent-memory-via-the-downstream-target-nrp1
#2
JOURNAL ARTICLE
Janina Kupke, Julien Klimmt, Franziska Mudlaff, Maximilian Schwab, Pavlo Lutsik, Christoph Plass, Carsten Sticht, Ana M M Oliveira
Epigenetic factors are well-established players in memory formation. Specifically, DNA methylation is necessary for the formation of long-term memory in multiple brain regions including the hippocampus. Despite the demonstrated role of DNA methyltransferases (Dnmts) in memory formation, it is unclear whether individual Dnmts have unique or redundant functions in long-term memory formation. Furthermore, the downstream processes controlled by Dnmts during memory consolidation have not been investigated. In this study, we demonstrated that Dnmt3a1, the predominant Dnmt in the adult brain, is required for long-term spatial object recognition and contextual fear memory...
March 18, 2024: Neuropsychopharmacology
https://read.qxmd.com/read/38490978/dual-inhibitors-of-dnmt-and-hdac-induce-viral-mimicry-to-induce-antitumour-immunity-in-breast-cancer
#3
JOURNAL ARTICLE
Wenjun Huang, Qingyun Zhu, Zhichao Shi, Yao Tu, Qinyuan Li, Wenwen Zheng, Zigao Yuan, Lulu Li, Xuyu Zu, Yue Hao, Bizhu Chu, Yuyang Jiang
The existing conventional treatments for breast cancer, including immune checkpoint blockade, exhibit limited effects in some cancers, particularly triple-negative breast cancer. Epigenetic alterations, specifically DNMT and HDAC alterations, are implicated in breast cancer pathogenesis. We demonstrated that DNMTs and HDACs are overexpressed and positively correlated in breast cancer. The combination of DNMT and HDAC inhibitors has shown synergistic antitumour effects, and our previously designed dual DNMT and HDAC inhibitor (termed DNMT/HDACi) 15a potently inhibits breast cancer cell proliferation, migration, and invasion and induces apoptosis in vitro and in vivo...
March 15, 2024: Cell Death Discovery
https://read.qxmd.com/read/38473715/knockdown-of-dnmt1-induces-slco3a1-to-promote-follicular-growth-by-enhancing-the-proliferation-of-granulosa-cells-in-mammals
#4
JOURNAL ARTICLE
Shuo Li, Liqing Zeng, Fen Miao, Nian Li, Weili Liao, Xiaofeng Zhou, Yongcai Chen, Hongyan Quan, Yingting He, Hao Zhang, Jiaqi Li, Xiaolong Yuan
In female mammals, the proliferation and apoptosis of granulosa cells (GCs) have been shown to determine the fate of follicles. DNA methyltransferases (DNMTs) and SLCO3A1 have been reported to be involved in the survival of GCs and follicular growth. However, the molecular mechanisms enabling DNMTs to regulate the expression of SLCO3A1 to participate in follicular growth are unclear. In this study, we found that the knockdown of DNMT1 enhanced the mRNA and protein levels of SLCO3A1 by regulating the chromatin accessibility probably...
February 20, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38469334/in-vitro-toxicity-of-lithium-bis-trifluoromethanesulfonyl-imide-litfsi-on-human-renal-and-hepatoma-cells
#5
JOURNAL ARTICLE
Xing Zhang, Mia Sands, Mindy Lin, Jennifer Guelfo, Joseph Irudayaraj
We evaluate the cytotoxicity, intracellular redox conditions, apoptosis, and methylation of DNMTs / TETs upon exposure to LiTFSI, a novel Per and Polyfluoroalkyl Substances (PFAS) commonly found in lithium-ion batteries, on human renal carcinoma cells (A498) and hepatoma cells (HepG2). The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay showed both Perfluorooctane sulfonate (PFOS) and Lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) had a dose-dependent effect on A498 and HepG2, with LiTFSI being less toxic...
June 2024: Toxicology Reports
https://read.qxmd.com/read/38464090/genome-wide-methylation-profiling-of-peripheral-t-cell-lymphomas-identifies-trip13-as-a-critical-driver-of-tumor-proliferation-and-survival
#6
Pawel Nowialis, Julian Tobon, Katarina Lopusna, Jana Opavska, Arshee Badar, Duo Chen, Reem Abdelghany, Gene Pozas, Jacob Fingeret, Emma Noel, Alberto Riva, Hiroshi Fujiwara, Rene Opavsky
Cytosine methylation of genomic DNA contributes to the regulation of gene expression and is involved in normal development including hematopoiesis in mammals. It is catalyzed by the family of DNA methyltransferases (DNMTs) that include DNMT1, DNMT3A, and DNMT3B. Peripheral T-cell lymphomas (PTCLs) represent a diverse group of aggressive mature T-cell malignancies accounting for approximately 10-15% of non-Hodgkin lymphoma cases in the US. PTCLs exhibit a broad spectrum of clinical, histological, and immunophenotypic features with poor prognosis and inadequately understood molecular pathobiology...
February 29, 2024: Research Square
https://read.qxmd.com/read/38457926/c-terminal-binding-protein-ctbp2-is-a-novel-tumor-suppressor-targeting-the-myc-irf4-axis-in-multiple-myeloma
#7
JOURNAL ARTICLE
Coty Hy Cheung, Chi Keung Cheng, Kam Tong Leung, Chi Zhang, Chi Yan Ho, Xi Luo, Angel Yf Kam, Tian Xia, Thomas Sk Wan, Herbert Augustus Pitts, Natalie Pui Ha Chan, Joyce Sin Cheung, Raymond Siu Ming Wong, Xiao-Bing Zhang, Margaret Hl Ng
Multiple myeloma (MM) cells are addicted to MYC and its direct transactivation target IRF4 for proliferation and survival. MYC and IRF4 are still considered "undruggable" as the majority of small molecule inhibitors suffers from low potency, suboptimal pharmacokinetic properties and undesirable off-target effects. Indirect inhibition of MYC/IRF4 emerges as a therapeutic vulnerability in MM. Here, we uncover an unappreciated tumor suppressive role of C-terminal Binding Protein 2 (CTBP2) in MM via strong inhibition of the MYC-IRF4 axis...
March 8, 2024: Blood Advances
https://read.qxmd.com/read/38447841/genome-wide-identification-evolution-of-dna-methyltransferases-and-their-expression-under-salinity-stress-in-larimichthys-crocea
#8
JOURNAL ARTICLE
Yu Zhang, Jiaqian Chen, Baoxiao Zheng, Jian Teng, Zhengjia Lou, Huijie Feng, Shiqi Zhao, Liangyi Xue
DNA methyltransferases (Dnmts) are responsible for DNA methylation which influences patterns of gene expression and plays a crucial role in response to environmental changes. In this study, 7 LcDnmt genes were identified in the genome of large yellow croaker (Larimichthys crocea). The comprehensive analysis was conducted on gene structure, protein and location site of LcDnmts. LcDnmt proteins belonged to three groups (Dnmt1, Dnmt2, and Dnmt3) according to their conserved domains and phylogenetic analysis. Although Dnmt3 can be further divided into three sub groups (Dnmt3a, Dnmt3b, and Dnmt3l), there is no Dnmnt3l member in the large yellow croaker...
March 4, 2024: International Journal of Biological Macromolecules
https://read.qxmd.com/read/38438051/from-molecular-pathogenesis-to-therapy-unraveling-non-coding-rnas-dnmt3a-axis-in-human-cancers
#9
REVIEW
Chunjie Huang, Seyed Mohsen Aghaei-Zarch
Cancer is a comprehensive classification encompassing more than 100 forms of malignancies that manifest in diverse tissues within the human body. Recent studies have provided evidence that aberrant epigenetic modifications are pivotal indicators of cancer. Epigenetics encapsulates DNA methyltransferases as a crucial class of modifiers. DNMTs, including DNMT3A, assume central roles in DNA methylation processes that orchestrate normal biological functions, such as gene transcription, predominantly in mammals...
March 2, 2024: Biochemical Pharmacology
https://read.qxmd.com/read/38425013/cracking-a-cancer-code-dna-methylation-in-epigenetic-modification-an-in-silico-approach-on-efficacy-assessment-of-sri-lanka-oriented-nutraceuticals
#10
JOURNAL ARTICLE
Dushanan R, Weerasinghe S, Dissanayake D P, Senthilnithy R
DNA methyltransferase (DNMTs) are essential epigenetic modifiers that play a critical role in gene regulation. These enzymes add a methyl group to cytosine's 5'-carbon, specifically within CpG dinucleotides, using S-adenosyl-L-methionine. Abnormal overexpression of DNMTs can alter the gene expression patterns and contribute to cancer development in the human body. Therefore, the inhibition of DNMT is a promising therapeutic approach to cancer treatment. This study was aimed to identify potential nutraceutical inhibitors from the Sri Lanka Flora database using computational methods, which provided an atomic-level description of the drug binding site and examined the interactions between nutraceuticals and amino acids of the DNMT enzyme...
February 29, 2024: Journal of Biomolecular Structure & Dynamics
https://read.qxmd.com/read/38395253/natural-bioactive-compounds-targeting-dna-methyltransferase-enzymes-in-cancer-mechanisms-insights-and-efficiencies
#11
REVIEW
Tarik Aanniz, Abdelhakim Bouyahya, Abdelaali Balahbib, Kawtar El Kadiri, Asaad Khalid, Hafiz A Makeen, Hassan A Alhazmi, Nasreddine El Omari, Younes Zaid, Rebecca Shin-Yee Wong, Chien Ing Yeo, Bey Hing Goh, Saad Bakrim
The regulation of gene expression is fundamental to health and life and is essentially carried out at the promoter region of the DNA of each gene. Depending on the molecular context, this region may be accessible or non-accessible (possibility of integration of RNA polymerase or not at this region). Among enzymes that control this process, DNA methyltransferase enzymes (DNMTs), are responsible for DNA demethylation at the CpG islands, particularly at the promoter regions, to regulate transcription. The aberrant activity of these enzymes, i...
February 21, 2024: Chemico-biological Interactions
https://read.qxmd.com/read/38376465/tunable-dnmt1-degradation-reveals-dnmt1-dnmt3b-synergy-in-dna-methylation-and-genome-organization
#12
JOURNAL ARTICLE
Andrea Scelfo, Viviana Barra, Nezar Abdennur, George Spracklin, Florence Busato, Catalina Salinas-Luypaert, Elena Bonaiti, Guillaume Velasco, Frédéric Bonhomme, Anna Chipont, Andréa E Tijhuis, Diana C J Spierings, Coralie Guérin, Paola Arimondo, Claire Francastel, Floris Foijer, Jӧrg Tost, Leonid Mirny, Daniele Fachinetti
DNA methylation (DNAme) is a key epigenetic mark that regulates critical biological processes maintaining overall genome stability. Given its pleiotropic function, studies of DNAme dynamics are crucial, but currently available tools to interfere with DNAme have limitations and major cytotoxic side effects. Here, we present cell models that allow inducible and reversible DNAme modulation through DNMT1 depletion. By dynamically assessing whole genome and locus-specific effects of induced passive demethylation through cell divisions, we reveal a cooperative activity between DNMT1 and DNMT3B, but not of DNMT3A, to maintain and control DNAme...
April 1, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38376279/role-of-curcumin-on-mir-26a-and-its-effect-on-dnmt1-dnmt3b-and-meg3-expression-in-a549-lung-cancer-cell
#13
JOURNAL ARTICLE
Zahra Mahmoudi, Mojtaba Jahani, Reza Nekouian
CONTEXT: Most of the patients diagnosed with non-small cell lung cancer (NSCLC) are in their advanced stages and as a result might not be cured in spite of the advances in aimed therapy. In the recent years, the role of noncoding RNAs (ncRNAs) has been expanded to cancer as potential targets for RNA-based epigenetic therapies. Curcumin, as an active ingredient, is associated with epigenetic alterations, and it might modulate the expression of tumor suppressor and oncogenic microRNAs. MATERIALS AND METHODS: In this study, we investigated the RNA-based epigenetic effects of curcumin on NSCLC, and the effect of curcumin on A549 cell viability was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay...
October 1, 2023: Journal of Cancer Research and Therapeutics
https://read.qxmd.com/read/38275760/tert-promoter-methylation-is-oxygen-sensitive-and-regulates-telomerase-activity
#14
JOURNAL ARTICLE
Fatma Dogan, Nicholas R Forsyth
Telomere repeats protect linear chromosomes from degradation, and telomerase has a prominent role in their maintenance. Telomerase has telomere-independent effects on cell proliferation, DNA replication, differentiation, and tumorigenesis. TERT (telomerase reverse transcriptase enzyme), the catalytic subunit of telomerase, is required for enzyme activity. TERT promoter mutation and methylation are strongly associated with increased telomerase activation in cancer cells. TERT levels and telomerase activity are downregulated in stem cells during differentiation...
January 19, 2024: Biomolecules
https://read.qxmd.com/read/38253156/cytotoxic-and-epigenetic-effects-of-berberine-loaded-chitosan-pectin-nanoparticles-on-ags-gastric-cancer-cells-role-of-the-mir-185-5p-klf7-axis-dnmts-and-global-dna-methylation
#15
JOURNAL ARTICLE
Esmaeel Babaeenezhad, Marzieh Rashidipour, Zohreh Jangravi, Mostafa Moradi Sarabi, Alireza Shahriary
Poor bioavailability, solubility, and absorption of berberine (Ber) limit its widespread application. Here, we formulated novel chitosan/pectin nanoparticles (NPs) loaded with Ber to address delivery problems and promote the anticancer properties of Ber in AGS gastric cancer cells. The ionic gelification method was used to synthesize NPs-Ber. Physicochemical characterization of NPs-Ber was performed using FE-SEM, DLS, PDI, ζ potential, and FTIR. The cytotoxic effects of NPs-Ber on AGS cells were evaluated using the MTT assay...
January 20, 2024: International Journal of Biological Macromolecules
https://read.qxmd.com/read/38231483/preclinical-evaluation-of-ntx-301-a-novel-dna-hypomethylating-agent-in-ovarian-cancer
#16
JOURNAL ARTICLE
Yinu Wang, Xiaolei Situ, Horacio Cardenas, Ellie Siu, Razzaq A Alhunayan, Russell Keathley, Edward Tanner, Jianjun Wei, Yuying Tan, Chinmayee Vallabh Prabhu Dessai, Ji-Xin Cheng, Daniela Matei
PURPOSE: DNA methylation causes silencing of tumor suppressor and differentiation-associated genes, being linked to chemoresistance. Previous studies demonstrated that hypomethylating agents (HMA) re-sensitize ovarian cancer (OC) to chemotherapy. NTX-301 is a highly potent and orally bioavailable HMA, in early clinical development. EXPERIMENTAL DESIGN: The anti-tumor effects of NTX-301 were studied in OC models by using cell viability, stemness and ferroptosis assays, RNA sequencing, lipidomic analyses and stimulated Raman spectroscopy...
January 17, 2024: Clinical Cancer Research
https://read.qxmd.com/read/38231285/dynamic-methylation-pattern-of-h19dmr-and-kvdmr1-in-bovine-oocytes-and-preimplantation-embryos
#17
JOURNAL ARTICLE
Carolina G Verruma, Renan S Santos, Jorge A P Marchesi, Sarah L A Sales, Reginaldo A Vila, Álvaro F L Rios, Cristiana L M Furtado, Ester S Ramos
PURPOSE: This study aimed to evaluate the epigenetic reprogramming of ICR1 (KvDMR1) and ICR2 (H19DMR) and expression of genes controlled by them as well as those involved in methylation, demethylation, and pluripotency. METHODS: We collected germinal vesicle (GV) and metaphase II (MII) oocytes, and preimplantation embryos at five stages [zygote, 4-8 cells, 8-16 cells, morula, and expanded blastocysts (ExB)]. DNA methylation was assessed by BiSeq, and the gene expression was evaluated using qPCR...
January 17, 2024: Journal of Assisted Reproduction and Genetics
https://read.qxmd.com/read/38216951/the-regulation-of-plasma-gelsolin-by-dna-methylation-in-ovarian-cancer-chemo-resistance
#18
JOURNAL ARTICLE
Hafiza Bushra Manzoor, Meshach Asare-Werehene, Satyajit Dey Pereira, Kapaettu Satyamoorthy, Benjamin K Tsang
BACKGROUND: Ovarian cancer (OVCA) is the most lethal gynecologic cancer and chemoresistance remains a major hurdle to successful therapy and survival of OVCA patients. Plasma gelsolin (pGSN) is highly expressed in chemoresistant OVCA compared with their chemosensitive counterparts, although the mechanism underlying the differential expression is not known. Also, its overexpression significantly correlates with shortened survival of OVCA patients. In this study, we investigated the methylation role of Ten eleven translocation isoform-1 (TET1) in the regulation of differential pGSN expression and chemosensitivity in OVCA cells...
January 12, 2024: Journal of Ovarian Research
https://read.qxmd.com/read/38204433/a-review-on-recent-advances-in-assays-for-dnmt1-a-promising-diagnostic-biomarker-for-multiple-human-cancers
#19
REVIEW
Yang Yu, Wen Fu, Yaxing Xie, Xue Jiang, Hong Wang, Xiaolan Yang
The abnormal expression of human DNA methyltransferases (DNMTs) is closely related with the occurrence and development of a wide range of human cancers. DNA (cytosine-5)-methyltransferase-1 (DNMT1) is the most abundant human DNA methyltransferase and is mainly responsible for genomic DNA methylation patterns. Abnormal expression of DNMT1 has been found in many kinds of tumors, and DNMT1 has become a valuable target for the diagnosis and drug therapy of diseases. Nowadays, DNMT1 has been found to be involved in multiple cancers such as pancreatic cancer, breast cancer, bladder cancer, lung cancer, gastric cancer and other cancers...
January 11, 2024: Analyst
https://read.qxmd.com/read/38200495/dna-mismatch-repair-system-regulates-the-expression-of-pd-l1-through-dnmts-in-cervical-cancer
#20
JOURNAL ARTICLE
Fan Guo, Ruijiao Lu, Weina Kong, Miyessar Anwar, Yangchun Feng
BACKGROUND: Cervical cancer (CC) is a potential clinical application of PD-1/PD-L1 inhibitor. We aimed to study the mechanism of DNA mismatch repair (MMR) system regulating the expression of PD-L1 in CC through DNA methyltransferase (DNMTs). METHODS: We collected pathological specimens from 118 cases of CC to analyze the relationship between PD-L1 expression and DNMTs in different MMR states. RNA interference (RNAi) technique was used to simulate the formation of CC cell line with MMR deficiency (dMMR) state, and subcutaneous tumor formation experiment was carried out in nude mice to verify the relationship between PD-L1 expression and DNMTs in MMR state...
January 10, 2024: Cancer Cell International
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