Re-expression of methylation-induced tumor suppressor gene silencing is associated with the state of histone modification in gastric cancer cell lines

Chunfeng,; Meng,; Xinjiang,; Zhu, Wanxue; Guo, Youguang; Peng, Peng; Dong-Qiu,; Dai, Ming

doi:10.3748/wjg.13.6166

Cited by 21 publications

(18 citation statements)

References 14 publications

(18 reference statements)

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“…H3K9Me2 histone dimethylation is a hallmark of gene silencing and was shown to mark silenced tumor suppressor genes [109][110][111]. H3K27Me3 methylation, which is targeted by EZH2, is another interesting target for inhibition.…”

Section: Histone Methylation Enzymes and Their Inhibitorsmentioning

confidence: 99%

Epigenetic Therapeutics in Autoimmune Disease

Szyf

2009

Clinic Rev Allerg Immunol

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Several lines of evidence suggest the involvement of disturbance in epigenetic processes in autoimmune disease. Most noteworthy is the global DNA hypomethylation seen in lupus. Epigenetic states in difference from genetic lesions are potentially reversible and hence candidates for pharmacological intervention. Potential targets for drug development are histone modification and DNA methylating and demethylating enzymes. The most advanced set of drugs in clinical development are histone deacetylase (HDAC) inhibitors. However, the prevalence of DNA hypomethylation in lupus suggests that we should shift our attention from HDAC inhibitors to DNA demethylation inhibitors. MBD2 was recently proposed to be involved in demethylation in T cells in lupus and is, therefore, a candidate target. Although this field is at its infancy, it carries great promise.

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Section: Histone Methylation Enzymes and Their Inhibitorsmentioning

confidence: 99%

Epigenetic Therapeutics in Autoimmune Disease

Szyf

2009

Clinic Rev Allerg Immunol

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“…28,29 Cells cultured in medium with DMSO was acted as a control. The cultured cells were harvested after indicated time points.…”

Section: Treatment Of Cell Lines With Demethylation and Histone Deacementioning

confidence: 99%

Hypermethylation of SOX2 Gene in Hydatidiform Mole and Choriocarcinoma

Siu

Zhang

et al. 2008

Reprod. Sci.

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This study investigated the expression and methylation profiles of SOX2, a stem cell-related transcription factor, in placentas and gestational trophoblastic disease. The methylation status of SOX2 promoter region in 55 hydatidiform moles, 4 choriocarcinoma, 23 first trimester, and 15 term placentas was evaluated by methylation-specific polymerase chain reaction. The methylated allele was found in 4.4% (1/23) of first trimester placentas, 26.7% (4/15) term placentas, and 56.4% (31/55) of hydatidiform moles and all choriocarcinoma samples and cell lines. A significant reduction in SOX2 messenger RNA expression was found in the hydatidiform moles (P = .027) when compared with that in the placentas. SOX2 messenger RNA expression was significantly correlated with SOX2 hypermethylation (P < .001). SOX2 expression was restored in choriocarcinoma cell lines following treatment to 5-Aza-2(')-deoxycytidine and/or Trichostatin A, demethylation and histone deacetylase inhibitors, respectively, and the response was synergistic. Epigenetic mechanisms may play important role on the transcriptional regulation of SOX2 and contribute to pathogenesis of gestational trophoblastic disease.

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“…DNA methylation induced silencing of hMLH1 has become the leading mechanism to account for the loss of detectable protein in tumors lacking mutations [16] . Our previous study reported that methylation of hMLH1 gene promoter induced the absence of hMLH1 expression in gastric cancer cell line [10] .…”

Section: Discussionmentioning

confidence: 99%

“…The ChIP assays were performed as described previously [10] . Briefly, proteins were cross-linked to DNA by addition of formaldehyde directly to the culture medium to a final concentration of 4g/l for 20 min at 37°C.…”

Section: Chipmentioning

confidence: 99%

Comparative evaluation of the effects of 5-Aza-2’-deoxycytidine and Trichostatin A on reactivation of hMLH1 in COC1/DDP ovarian cancer cell line

Meng

Dai

2009

Chin. J. Cancer Res.

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Objective: hMLH1 protein serves to detect the DNA damage caused by cisplatin (DDP) and destroys the cell. The absence of hMLH1 expression has been correlated with acquired resistance of ovarian cancer cells to platinum. The aim of this study was to determine the possible role of DNA methylation and histone H3 lysine 9 (H3-K9) acetylation on the loss of hMLH1 expression, and to evaluate the reversal effects of 5-Aza-2'-deoxycytidine (5-Aza-dC) and Trichostatin A (TSA) on DDP-resistance in ovarian cancer cell lines.Methods: Two human ovarian cancer cell lines, COC1 and its DDP-resistant subline, COC1/DDP were cultured. The two cancer cells were treated with 5-Aza-dC or TSA. Using COC1 cells as a control, we used methylation-specific PCR (MSP) to analyze DNA methylation at hMLH1 gene promoter. hMLH1 mRNA and protein expressions were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot. Chromatin immunoprecipitation assay (ChIP) was used to test the levels of histone H3-K9 acetylation at hMLH1 gene promoter.Results: In COC1 cells, there was no DNA methylation at hMLH1 gene promoter, while there were hMLH1 mRNA and protein expression. In COC1/DDP cells, there was DNA hypermethylation at hMLH1 gene promoter, while there was no hMLH1 mRNA or protein expression. The treatment with 5-Aza-dC resulted in DNA demethylation at the promoter region, as well as restoration of hMLH1 expression in COC1/DDP cells. The treatment with TSA had no effects on DNA demethylation or restoration of hMLH1 expression in COC1/DDP cells.Conclusion: Hypermethylation of DNA at the promoter is related to the silencing of hMLH1 in COC1/DDP ovarian cancer cells. DNA methylation at hMLH1 promoter could play a significant role in determining the sensitivity of ovarian cancer to DDP. The drug resistance mediated by methylation of hMLH1 could be overcome by 5-Aza-dC.

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Re-expression of methylation-induced tumor suppressor gene silencing is associated with the state of histone modification in gastric cancer cell lines

Cited by 21 publications

References 14 publications

Epigenetic Therapeutics in Autoimmune Disease

Epigenetic Therapeutics in Autoimmune Disease

Hypermethylation of SOX2 Gene in Hydatidiform Mole and Choriocarcinoma

Comparative evaluation of the effects of 5-Aza-2’-deoxycytidine and Trichostatin A on reactivation of hMLH1 in COC1/DDP ovarian cancer cell line

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