scholarly journals DNA Methylation Activates TP73 Expression in Hepatocellular Carcinoma and Gastrointestinal Cancer

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Zhixing Yao ◽  
Cristina Di Poto ◽  
Grace Mavodza ◽  
Everett Oliver ◽  
Habtom W. Ressom ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cell Lines ◽  
Cancer Cell ◽  
Gastrointestinal Cancer ◽  
Normal Skin ◽  
Hepatocellular Cancer ◽  
Normal Liver ◽  
Cancer Cell Lines ◽  
Specific Pcr ◽  
Liver Tissues

AbstractThe complexity of TP73 expression and its functionality, as well as the role of TP73 in tumorigenesis, unlike its cousin TP53, which is an established tumor suppressor, have remained elusive to date. In this study, we isolated two stem cell lines (HepCY & HepCO) from normal young and old human liver tissues. We determined TP73 expression in HepCY and HepCO, hepatocellular cancer (HCC) cell lines (HepG2, SNU398, SNU449 and SNU475), gastrointestinal cancer (GI) cell lines (Caco2 and HCT116) and normal skin fibroblasts cell line (HS27). Immunohistochemical analyses of TP73 expression was also performed in non-cancerous and adjacent cancerous liver tissues of HCC patients. The results show that TP73 expression is exclusive to the cancer cell lines and not the adjacent normal liver tissues. Moreover, methylation-specific PCR and bisulfite sequencing studies revealed that TP73 promoter is activated only in cancer cell lines by DNA methylation. Furthermore, ChIP assay results demonstrated that a chromosomal networking protein (CTCF) and tumor protein p53 (TP53) bind to TP73 promoter and regulate TP73 expression. Our observations demonstrate that a positive correlation in tumorigenesis exists between TP73 expression and DNA methylation in promoter regions of TP73. These findings may prove significant for the development of future diagnostic and therapeutic applications.

scholarly journals Association of expression of epigenetic molecular factors with DNA methylation and sensitivity to chemotherapeutic agents in cancer cell lines

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Suleyman Vural ◽  
Alida Palmisano ◽  
William C. Reinhold ◽  
Yves Pommier ◽  
Beverly A. Teicher ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antitumor Agents ◽  
Cancer Cell Lines ◽  
Chemotherapeutic Agents ◽  
Epigenetic Factors ◽  
Expression Of Genes ◽  
Genes Encoding

Abstract Background Altered DNA methylation patterns play important roles in cancer development and progression. We examined whether expression levels of genes directly or indirectly involved in DNA methylation and demethylation may be associated with response of cancer cell lines to chemotherapy treatment with a variety of antitumor agents. Results We analyzed 72 genes encoding epigenetic factors directly or indirectly involved in DNA methylation and demethylation processes. We examined association of their pretreatment expression levels with methylation beta-values of individual DNA methylation probes, DNA methylation averaged within gene regions, and average epigenome-wide methylation levels. We analyzed data from 645 cancer cell lines and 23 cancer types from the Cancer Cell Line Encyclopedia and Genomics of Drug Sensitivity in Cancer datasets. We observed numerous correlations between expression of genes encoding epigenetic factors and response to chemotherapeutic agents. Expression of genes encoding a variety of epigenetic factors, including KDM2B, DNMT1, EHMT2, SETDB1, EZH2, APOBEC3G, and other genes, was correlated with response to multiple agents. DNA methylation of numerous target probes and gene regions was associated with expression of multiple genes encoding epigenetic factors, underscoring complex regulation of epigenome methylation by multiple intersecting molecular pathways. The genes whose expression was associated with methylation of multiple epigenome targets encode DNA methyltransferases, TET DNA methylcytosine dioxygenases, the methylated DNA-binding protein ZBTB38, KDM2B, SETDB1, and other molecular factors which are involved in diverse epigenetic processes affecting DNA methylation. While baseline DNA methylation of numerous epigenome targets was correlated with cell line response to antitumor agents, the complex relationships between the overlapping effects of each epigenetic factor on methylation of specific targets and the importance of such influences in tumor response to individual agents require further investigation. Conclusions Expression of multiple genes encoding epigenetic factors is associated with drug response and with DNA methylation of numerous epigenome targets that may affect response to therapeutic agents. Our findings suggest complex and interconnected pathways regulating DNA methylation in the epigenome, which may both directly and indirectly affect response to chemotherapy.

scholarly journals Recurrent patterns of DNA methylation in theZNF154,CASP8, andVHLpromoters across a wide spectrum of human solid epithelial tumors and cancer cell lines

Epigenetics ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. 1355-1372 ◽  
Author(s):  
Francisco Sánchez-Vega ◽  
Valer Gotea ◽  
Hanna M Petrykowska ◽  
Gennady Margolin ◽  
Thomas C Krivak ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cell Lines ◽  
Cancer Cell ◽  
Wide Spectrum ◽  
Cancer Cell Lines ◽  
Epithelial Tumors ◽  
Recurrent Patterns

scholarly journals Micro-RNA-181a regulates osteopontin-dependent metastatic function in hepatocellular cancer cell lines

Surgery ◽  
2010 ◽  
Vol 148 (2) ◽  
pp. 291-297 ◽  
Author(s):  
Syamal D. Bhattacharya ◽  
Juline Garrison ◽  
Hongtao Guo ◽  
Zhiyong Mi ◽  
Jovan Markovic ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Hepatocellular Cancer ◽  
Cancer Cell Lines ◽  
Micro Rna

scholarly journals Hemimethylation Patterns in Breast Cancer Cell Lines

2019 ◽  
Vol 18 ◽  
pp. 117693511987295 ◽  
Author(s):  
Shuying Sun ◽  
Yu Ri Lee ◽  
Brittany Enfield
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Tumor Growth ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Entire Genome ◽  
Cpg Sites

DNA methylation is an epigenetic event that involves adding a methyl group to the cytosine (C) site, especially the one that pairs with a guanine (G) site (ie, CG or CpG site), in a human genome. This event plays an important role in both cancerous and normal cell development. Previous studies often assume symmetric methylation on both DNA strands. However, asymmetric methylation, or hemimethylation (methylation that occurs only on 1 DNA strand), does exist and has been reported in several studies. Due to the limitation of previous DNA methylation sequencing technologies, researchers could only study hemimethylation on specific genes, but the overall genomic hemimethylation landscape remains relatively unexplored. With the development of advanced next-generation sequencing techniques, it is now possible to measure methylation levels on both forward and reverse strands at all CpG sites in an entire genome. Analyzing hemimethylation patterns may potentially reveal regions related to undergoing tumor growth. For our research, we first identify hemimethylated CpG sites in breast cancer cell lines using Wilcoxon signed rank tests. We then identify hemimethylation patterns by grouping consecutive hemimethylated CpG sites based on their methylation states, methylation “M” or unmethylation “U.” These patterns include regular (or consecutive) hemimethylation clusters (eg, “MMM” on one strand and “UUU” on another strand) and polarity (or reverse) clusters (eg, “MU” on one strand and “UM” on another strand). Our results reveal that most hemimethylation clusters are the polarity type, and hemimethylation does occur across the entire genome with notably higher numbers in the breast cancer cell lines. The lengths or sizes of most hemimethylation clusters are very short, often less than 50 base pairs. After mapping hemimethylation clusters and sites to corresponding genes, we study the functions of these genes and find that several of the highly hemimethylated genes may influence tumor growth or suppression. These genes may also indicate a progressing transition to a new tumor stage.

High concordance between DNA methylation of tumor suppressor loci in pancreatic cancer cell lines and their corresponding primary carcinoma

2000 ◽  
Vol 118 (4) ◽  
pp. A46
Author(s):  
Takashi Ueki ◽  
Minoru Toyota ◽  
Kimberly M. Walter ◽  
Elizabeth Jaffee ◽  
Charles J. Yeo ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Dna Methylation ◽  
Tumor Suppressor ◽  
Cell Lines ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Cancer Cell Lines ◽  
Primary Carcinoma ◽  
High Concordance

Translational disequilibrium as an interference marker to study miRNA and methylation silencing of APRIN, a stem cell regulator in breast cancer microchimerism

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11109-11109
Author(s):  
P. Geck ◽  
V. Denes ◽  
M. Pilichowska ◽  
A. Makarovskiy ◽  
G. A. Carpinito
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Stem Cell ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Fetal Microchimerism ◽  
Clinical Breast

11109 Background: Gene silencing is universally observed in cancer and involves promoter DNA methylation. We found that a cohesin-related stem cell regulator, APRIN (Pds5B) was silenced in breast cancer clinical samples. Surprisingly, in 40% of these samples DNA methylation was not involved. Furthermore, in some breast cancer cell lines the APRIN protein was silenced without transcript downregulation or promoter methylation. This “translational disequilibrium” has been frequently reported with other proteins, but without mechanistic explanations. Recent results with RNA interference indicate that gene repression through microRNAs (typically mismatched) is mostly translational without transcript degradation. We propose, therefore, that the puzzling translational disequilibrium phenomenon is a new form of epigenetic silencing by miRNA mechanisms. We aim (i) to verify miRNA epigenetics of APRIN silencing in breast cancer cell lines; (ii) to study clinical breast cancer samples for methylation vs. miRNAs mechanisms in APRIN translational disequilibrium; and (iii) to investigate if miRNA silencing of APRIN affects a fetal embryonic stem cell pool in breast cancer (microchimerism). Methods: (i) We used miRNA mimics and miRNA inhibitors in breast cancer cell lines to verify specific miRNA involvement in APRIN silencing. (ii) We used immunohistochemistry with bisulfite converted DNA for methylation and microdissected RNA for microRNA interference studies from 56 clinical breast cancer samples. (iii) We used Y-chromosome markers on microdissected DNA for fetal microchimerism studies. Results: (i) We found that in breast cancer cell lines with APRIN translational disequilibrium a set of microRNAs correlate with APRIN silencing. (ii) We found miRNA related mechanisms in about 35 percent of breast cancer samples where APRIN was silenced and (iii) APRIN may specifically affect stem cells of fetal origin in the mother's mammary gland and contribute to cancer. Conclusions: The novel miRNA-based mechanism maybe a new epigenetic factor of gene silencing in cancer. We experimentally confirmed a set of APRIN specific miRNAs and established preliminary correlations with fetal microchimerism in breast cancer. No significant financial relationships to disclose.

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