• Molecules and Cells
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• v.44 no.3
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• pp.146-159
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• 2021

DNA methylation, and consequent down-regulation, of tumour suppressor genes occurs in response to epigenetic stimuli during cancer development. Similarly, human oncoviruses, including human papillomavirus (HPV), up-regulate and augment DNA methyltransferase (DNMT) and histone deacetylase (HDAC) activities, thereby decreasing tumour suppressor genes (TSGs) expression. Ubiquitin-like containing PHD and RING finger domain 1 (UHRF1), an epigenetic regulator of DNA methylation, is overexpressed in HPV-induced cervical cancers. Here, we investigated the role of UHRF1 in cervical cancer by knocking down its expression in HeLa cells using lentiviral-encoded short hairpin (sh)RNA and performing cDNA microarrays. We detected significantly elevated expression of thioredoxin-interacting protein (TXNIP), a known TSG, in UHRF1-knockdown cells, and this gene is hypermethylated in cervical cancer tissue and cell lines, as indicated by whole-genome methylation analysis. Up-regulation of UHRF1 and decreased TXNIP were further detected in cervical cancer by western blot and immunohistochemistry and confirmed by Oncomine database analysis. Using chromatin immunoprecipitation, we identified the inverted CCAAT domain-containing UHRF1-binding site in the TXNIP promoter and demonstrated UHRF1 knockdown decreases UHRF1 promoter binding and enhances TXNIP expression through demethylation of this region. TXNIP promoter CpG methylation was further confirmed in cervical cancer tissue by pyrosequencing and methylation-specific polymerase chain reaction. Critically, down-regulation of UHRF1 by siRNA or UHRF1 antagonist (thymoquinone) induces cell cycle arrest and apoptosis, and ubiquitin-specific protease 7 (USP7), which stabilises and promotes UHRF1 function, is increased by HPV viral protein E6/E7 overexpression. These results indicate HPV might induce carcinogenesis through UHRF1-mediated TXNIP promoter methylation, thus suggesting a possible link between CpG methylation and cervical cancer.

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.10b
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• pp.152-152
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• 2003

Cytochrome P450 1A2 (CYP1A2) is constitutively and inducibly expressed preferentially in liver of mice, but the molecular mechanisms underlying the expression of CYP1A2 have not yet been fully clarified. In this study, CpG sites of the Cyp1a2 promoter in liver were found to be hypomethylated in a site-specific pattern compared to those in lung and kidney.(omitted)

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.431-437
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• 2016

In this investigation, global DNA methylation patterns and the specific methylation status of 5 genes were studied in DNA from peripheral blood (PB) and impact on progression free survival (PFS) and overall-survival (OS) in patients with de novo or relapsed acute myeloid leukemia (AML) treated with decitabine-based regimens waas assessed. DNA was isolated from PB samples at the time of -1, 1, and 7 days of chemotherapy. Global methylation was determined by ELISA, and the CpG island DNA methylation profile of 5 genes using a DNA methylation PCR system. Our data demonstrated that patients with a high level of 5-mC had a poor prognosis after demethylation therapy and those who have low levels of 5-mC in PB achieved higher CR and better SO, but there was no significant correlation found between the 5-mC levels and other clinical features before treatment except the disease status. Higher methylation status of Sox2 and Oct4 genes was associated with differential response to demethylation therapy. A relatively low methylation percentage in one or both of these two genes was also associated with longer OS after decitabine based chemotherapy. We also suggest that global DNA and Oct-4/Sox2 methylation might impact on the pathogenesis of leukemia and play an important role in the initiation and progression. Moreover, dynamic analysis of 5-mC and Oct-4/Sox2 in peripheral blood nucleated cells of leukemia patients may provide clues to important molecular diagnostic and prognostic targets.

• Korean Journal of Medicinal Crop Science
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• v.12 no.1
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• pp.60-66
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• 2004

This study was carried out to confirm the phylogenetic relationships in Korean Rhus species. Sequences from internal transcribed spacers (ITS) of nuclear ribosomal DNA and rbcL gene of chloroplast DNA were determined. Cotinus coggygria was selected as outgroup because it is closest allied with Rhus in Anacardiaceae. Also, ingroup was limited as six Korean Rhus species. ITS 1 sequences in six species of Rhus and one species of Cotinus ranged from 246 to 253 bp and ITS 2 sequences from 234 to 244 bp. Concerning the G+C content of the studied taxa, ITS 1 sequences ranged from 58.0 to 68.13% and ITS 2 from 59.75 to 68.46%. On the other hand, rbcL sequences were same size in the all species examined by 1,428 bp. G+C contents of rbcL sequences were ranged from 43.56 to 43.77% which means there are nearly no different from interspecies each other. Phylogenetic tree strongly supports the colse relationships between R. succedanea and R. sylvestris. Rhus javanica and Cotinus coggygria were also closely allied with each other in ITS and rbcL trees. Therefore, R. javanica was regarded as most primitive species among the Korean Rhus species. ITS 1 region of nuclear ribosomal DNA was suggested as very useful taxonomical marker for genus Rhus.

• The Korean Journal of Applied Statistics
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• v.29 no.6
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• pp.1117-1128
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• 2016

In genetic association studies with high-dimensional genomic data, regularization procedures based on penalized likelihood are often applied to identify genes or genetic regions associated with diseases or traits. A network-based regularization procedure can utilize biological network information (such as genetic pathways and signaling pathways in genetic association studies) with an outstanding selection performance over other regularization procedures such as lasso and elastic-net. However, network-based regularization has a limitation because cannot be applied to high-dimension genomic data with a group structure. In this article, we propose to combine data dimension reduction techniques such as principal component analysis and a partial least square into network-based regularization for the analysis of high-dimensional genomic data with a group structure. The selection performance of the proposed method was evaluated by extensive simulation studies. The proposed method was also applied to real DNA methylation data generated from Illumina Innium HumanMethylation27K BeadChip, where methylation beta values of around 20,000 CpG sites over 12,770 genes were compared between 123 ovarian cancer patients and 152 healthy controls. This analysis was also able to indicate a few cancer-related genes.

• Asian-Australasian Journal of Animal Sciences
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• v.29 no.7
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• pp.1037-1043
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• 2016

Epigenetic processes in the development of skeletal muscle have been appreciated for over a decade. DNA methylation is a major epigenetic modification important for regulating gene expression and suppressing spurious transcription. Up to now, the importance of epigenetic marks in the regulation of Pax7 and myogenic regulatory factors (MRFs) expression is far less explored. In the present study, semi-quantitative the real-time polymerase chain reaction (RT-PCR) analyses showed MyoD and Myf5 were expressed in activated and quiescent C2C12 cells. MyoG was expressed in a later stage of myogenesis. Pax7 was weakly expressed in differentiated C2C12 cells. To further understand the regulation of expression of these genes, the DNA methylation status of Pax7, MyoD, and Myf5 was determined by bisulfite sequencing PCR. During the C2C12 myoblasts fusion process, the changes of promoter and exon 1 methylation of Pax7, MyoD, and Myf5 genes were observed. In addition, an inverse relationship of low methylation and high expression was found. These results suggest that DNA methylation may be an important mechanism regulating Pax7 and MRFs transcription in cell myogenic differentiation.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2209-2213
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• 2015

DNA methylation of tumor suppressor gene promoters is the most frequent phenomenon leading to inactivation of function, consequently driving malignant cell transformation. Cyclin D2 is implicated in tumor suppression. In our study, we carried out the MSP assay to evaluation the methylation status at CpG islands in the cyclin D2 promoter in breast cancer cases from the Vietnamese population. The results showed that the frequency of methylation reached 62.1% (59 of 95 breast cancer tumors), but was low in non-cancer specimens at 10% (2 of 20 non-cancer specimens). Additionally, with an RR (relative risk) and OR (odd ratios) of 6.21 and 14.8, DNA hypermethylation of cyclin D2 increased the possibility of malignant transformation. Our results confirmed the cyclin D2 hypermethylation could be used as the potential biomarker which could be applied in prognosis and early diagnosis of Vietnamese breast cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.3959-3962
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• 2016

The ten-eleven-translocation-2 (TET2) gene is a novel tumor suppressor gene involved in several hematological malignancies of myeloid and lymphoid origin. Besides loss-of-function mutations and deletions, hypermethylation of the CpG island at the TET2 promoter has been found in human cancers. The TET2 encoded protein regulates DNA methylation. The present study aimed to examine DNA promoter methylation of TET2 in 100 childhood acute lymphoblastic leukemia (ALL) cases and 120 healthy children in southeast Iran. In addition, mRNA expression levels were assessed in 30 new cases of ALL and 32 controls. Our ndings indicated that promoter methylation of TET2 signi cantly increases the risk of ALL (OR=2.60, 95% CI=1.31-5.12, p=0.0060) in comparison with absent methylation. Furthermore, the TET2 gene was signi cantly downregulated in childhood ALL compared to healthy children (p=0.0235). The results revealed that hypermethylation and downregulation of TET2 gene may play a role in predisposition to childhood ALL. Further studies with larger sample sizes and different ethnicities are needed to con rm our ndings.

• Asian-Australasian Journal of Animal Sciences
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• v.21 no.11
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• pp.1572-1575
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• 2008

The xenotransplantation of pig organs and cells can be related with a risk of transmission of infectious diseases to human. Previous findings indicate that the regulatory region of PERV for retroviral transcription, replication and integration into the cellular DNA is located on the 5' Long Terminal Repeat (LTR). The objective of this study is the investigation of methylation and deletion status of the PERV 5' LTR region which can be used for regulating PERV expression. We compared the sequences of genomic DNA and bisulfite-treated genomic DNA from PK-15 cells expressing PERV to observe the methylation status of the 5' LTR. Our results showed that the CpG sites of U3 were methylated and methylation was inconsistent in the R and U5 regions. Also, variable numbers of 18 bp repeats and 21 bp repeats were detected on 5' LTR by sequencing analysis. The consistent U3 methylation might be indicative of host suppression of expression of the retroviruses.

• Journal of Plant Biotechnology
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• v.43 no.4
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• pp.417-421
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• 2016

The complete chloroplast genome sequence of Panax ginseng breeding line 'G07006', showing higher salt tolerance, was confirmed by de novo assembly using whole genome next-generation sequences. The complete chloroplast (CP) genome size is 156,356 bp, including two inverted repeats (IRs) of 52,060 bp, separated by the large single-copy (LSC 86,174 bp) and the small single-copy (SSC 18,122 bp) regions. One hundred fourteen genes were annotated, including 80 protein-coding genes, 30 tRNA genes, and 4 rRNA genes. Among them, 18 sites were duplicated in the inverted repeat regions. By comparative analyses of the previously identified CP genome sequences of nine cultivars of P. ginseng and that of G07006, five useful SNPs were defined in this study. Since three of the five SNPs were cultivar-specific to Chunpoong and Sunhyang, they could be easily used for distinguishing from other ginseng accessions. However, on arranging SNPs according to their gene location, the G07006 genotype was 'GTGGA', which was distinct from other accessions. This complete chloroplast DNA sequence could be conducive to discrimination of the line G07006 (salt-tolerant) and further enhancement of the genetic improvement program for this important medicinal plant.