Identification and investigation of methylated genes in hepatoma

Chiba, Tetsuhiro; Yokosuka, Osamu; Fukai, Kenichi; Hirasawa, Yuichi; Tada, Motohisa; Mikata, Rintaro; Imazeki, Fumio; Taniguchi, Hideki; Iwama, Atsushi; Miyazaki, Masaru; Ochiai, Takenori; Saisho, Hiromitsu

doi:10.1016/j.ejca.2005.02.014

Cited by 46 publications

(42 citation statements)

References 30 publications

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“…The down-regulation of FN gene expression through the hypermethylation of 59CpG islands in its promoter region has been suggested to play a functional role in the development and progression of certain malignancies (26). We evaluated the extent of CpG methylation in the FN promoter as well as 100 bp upstream of the transcriptional start site in pAEC AA using direct sequencing of bisulfite-converted genomic DNA.…”

Section: The Fn Promoter Is Not Epigenetically Silenced In Paec Aamentioning

confidence: 99%

Decreased Fibronectin Production Significantly Contributes to Dysregulated Repair of Asthmatic Epithelium

Kicic¹,

Hallstrand²,

Sutanto³

et al. 2010

Am J Respir Crit Care Med

137

154

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Rationale: Damage to airway epithelium is followed by deposition of extracellular matrix (ECM) and migration of adjacent epithelial cells. We have shown that epithelial cells from children with asthma fail to heal a wound in vitro. Objectives: To determine whether dysregulated ECM production by the epithelium plays a role in aberrant repair in asthma. Methods: Airway epithelial cells (AEC) from children with asthma (n 5 36), healthy atopic control subjects (n 5 23), and healthy nonatopic control subjects (n 5 53) were investigated by microarray, gene expression and silencing, transcript regulation analysis, and ability to close mechanical wounds. Measurements and Main Results: Time to repair a mechanical wound in vitro by AEC from healthy and atopic children was not significantly different and both were faster than AEC from children with asthma. Microarray analysis revealed differential expression of multiple gene sets associated with repair and remodeling in asthmatic AEC. Fibronectin (FN) was the only ECM component whose expression was significantly lower in asthmatic AEC. Expression differences were verified by quantitative polymerase chain reaction and ELISA, and reduced FN expression persisted in asthmatic cells over passage. Silencing of FN expression in nonasthmatic AEC inhibited wound repair, whereas addition of FN to asthmatic AEC restored reparative capacity. Asthmatic AEC failed to synthesize FN in response to wounding or cytokine/ growth factor stimulation. Exposure to 59, 29deoxyazacytidine had no effect on FN expression and subsequent analysis of the FN promoter did not show evidence of DNA methylation. Conclusions: These data show that the reduced capacity of asthmatic epithelial cells to secrete FN is an important contributor to the dysregulated AEC repair observed in these cells.

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Section: The Fn Promoter Is Not Epigenetically Silenced In Paec Aamentioning

confidence: 99%

Decreased Fibronectin Production Significantly Contributes to Dysregulated Repair of Asthmatic Epithelium

Kicic¹,

Hallstrand²,

Sutanto³

et al. 2010

Am J Respir Crit Care Med

137

154

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“…Consistent with this, among the top 100 genes for which regulation is probably evolving under stabilizing selection, genes associated with human cancer are slightly enriched (9% compared to 5% in the total gene sample; P ¼ 0.10, one-tailed Fisher's exact test). Moreover, the expression levels of five genes (MBD4, WWOX, ING1, ATP7B and IGFBP2; ranked 5th, 12th, 28th, 58th and 66th, respectively) have been shown to be altered specifically in liver carcinoma [21][22][23][24] . These Figure 1 | Expression changes in specific lineages.…”

Section: Lettersmentioning

confidence: 99%

Expression profiling in primates reveals a rapid evolution of human transcription factors

Gilad

Oshlack

Smyth

et al. 2006

Nature

285

253

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Although it has been hypothesized for thirty years that many human adaptations are likely to be due to changes in gene regulation 1 , almost nothing is known about the modes of natural selection acting on regulation in primates. Here we identify a set of genes for which expression is evolving under natural selection. We use a new multi-species complementary DNA array to compare steady-state messenger RNA levels in liver tissues within and between humans, chimpanzees, orangutans and rhesus macaques. Using estimates from a linear mixed model, we identify a set of genes for which expression levels have remained constant across the entire phylogeny (,70 million years), and are therefore likely to be under stabilizing selection. Among the top candidates are five genes with expression levels that have previously been shown to be altered in liver carcinoma. We also find a number of genes with similar expression levels among non-human primates but significantly elevated or reduced expression in the human lineage, features that point to the action of directional selection. Among the gene set with a human-specific increase in expression, there is an excess of transcription factors; the same is not true for genes with increased expression in chimpanzee.A number of recent studies have used DNA microarrays to compare patterns of gene expression between closely related species 2-9 . Within primates, the focus has been primarily on human-chimpanzee comparisons, estimating gene expression profiles for a number of tissues, including liver, brain and heart 2,6,7,10 . The aim has been to characterize general trends in the evolution of gene expression rather than to identify specific genes of interest. To date, conclusions about the selection pressures acting on gene expression have been conflicting 2,3,6,[11][12][13] .These studies have all relied on data collected from arrays using gene probes that were designed on the basis of human sequences only. However, sequence mismatches affect hybridization intensity and can therefore bias estimates of gene expression differences between species 14 . This limitation of single-species arrays is especially problematic when the goal is to study how expression changes over evolutionary time. To make comparisons between more distantly related primate species, we generated a multi-species cDNA array that allows comparison of gene expression between species without the confounding effects of sequence divergence 14 . This cDNA array contains probes for 1,056 orthologous genes from four species (see Supplementary Methods) 14 .We used this array to compare gene expression profiles in the livers of humans, chimpanzees (Pan troglodytes), orangutans (Pongo pygmaeus) and rhesus macaques (Macaca mulatta), the phylogeny of which represents approximately 70 million years (Myr) of evolution. By assigning expression changes in the liver to particular lineages, we were able to identify the first set of genes for which regulation seems to be under lineage-specific selection pressures. In order to measure gene...

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“…In previous studies, we evaluated the genes in hepatoma cells that were up-regulated after 5-AzaC administration. 11,12 To gain a more comprehensive view of the sequential gene changes caused by 5-AzaC treatment, we evaluated gene expression levels at several time points posttreatment by microarray analysis. In the current study, we monitored the changes in messenger RNA (mRNA) levels every 24 hours up to 120 hours after 5-AzaC treatment.…”

mentioning

confidence: 99%

Sequential gene expression changes in cancer cell lines after treatment with the demethylation agent 5‐Aza‐2′‐deoxycytidine

Arai

Yokosuka

Hirasawa

et al. 2006

Cancer

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Pristine‐, poly(octafluorotoluene)‐ (POFT), and polyacetylene (PAc)‐coated Si wafers were used as substrates for the study of segregation of silicone diacrylate (SA) from a formulation containing other oligomeric and monomeric acrylates. POFT and PAc were microwave plasma polymerized on the Si wafers. Three SAs with molecular weights ranging from 700 to 6000 Da were synthesized and characterized. Formulations with 2 wt % SA were ultraviolet cured on the silicon wafers. The surface composition of formulation‐substrate side of the cured film was analyzed with X‐ray photoelectron spectroscopy, and the depth profile was analyzed with time of flight‐secondary ion mass spectrometry. The analysis results indicated that SA aggregated on all three types of Si surfaces. However, SA segregation is highest on the low surface energy POFT‐coated Si substrate, and low‐molecular‐weight SA is favorable to the segregation. For high‐molecular‐weight SA, the different Si substrates do not affect the degree of aggregation at the formulation‐substrate interface. The observed SA aggregation trend can be predicted by the Gibbs‐adsorption equation correlated to the resin surface tension and contact angle on substrates. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 48: 442–450, 2010

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Identification and investigation of methylated genes in hepatoma

Cited by 46 publications

References 30 publications

Decreased Fibronectin Production Significantly Contributes to Dysregulated Repair of Asthmatic Epithelium

Decreased Fibronectin Production Significantly Contributes to Dysregulated Repair of Asthmatic Epithelium

Expression profiling in primates reveals a rapid evolution of human transcription factors

Sequential gene expression changes in cancer cell lines after treatment with the demethylation agent 5‐Aza‐2′‐deoxycytidine

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