Abstract:
:Aberrant DNA methylation on CpG islands is one of the most consistent epigenetic changes in human cancers, and the methylation process is catalyzed by DNA methyltransferase (DNMT). We evaluated i) the mRNA levels of three DNMTs; DNMT1, DNMT3a and DNMT3b, in 25 hepatocellular carcinomas (HCCs), in their corresponding non-cancerous liver tissues and in 7 normal livers by using real-time reverse transcriptase-polymerase chain reaction; ii) nuclear expression of DNMT1 and DNMT3a proteins in the HCCs by immunohistochemistry, iii) the methylation status of 5 genes; p16, p15, E-cadherin, HIC-1 and RASSF1A in the same tissues, and iv) the relationships between the above results and the clinicopathological characteristics, including prognosis. The differences in mRNA expression levels for DNMT1, DNMT3a and DNMT3b were statistically significant between HCC and normal livers (p<0.001), HCC and chronic hepatitis (p<0.001) and HCC and cirrhosis (p<0.001). An increase in mRNA expression levels of >4-fold for DNMT3b in HCCs was significantly associated with a poorer overall survival (p=0.027) and shorter metastasis-free survival (p=0.0299). A poorer recurrence-free survival was noted in HCCs with a >4-fold increase in DNMT3a mRNA (p=0.0120). The average numbers of methylated genes were 0, 1.27, 1.38 and 2.72 for normal livers, chronic hepatitis, cirrhosis and HCCs, respectively, and this progressive increase from normal livers to chronic hepatitis/cirrhosis through HCC may suggest that tumor suppressor gene methylation is an early event in hepatocarcinogenesis. These results first suggest that hepatocarcinogenesis involves an increased expression of DNMT1, DNMT3a and DNMT3b mRNA and a progressive increase in the number of methylated genes from normal liver, chronic hepatitis/cirrhosis to HCC and secondly that an increase in the DNMT3a and DNMT3b mRNA levels in HCCs relative to their non-cancerous tissues may be a predictor of poor survival.
journal_name
Int J Mol Medjournal_title
International journal of molecular medicineauthors
Oh BK,Kim H,Park HJ,Shim YH,Choi J,Park C,Park YNsubject
Has Abstractpub_date
2007-07-01 00:00:00pages
65-73issue
1eissn
1107-3756issn
1791-244Xjournal_volume
20pub_type
杂志文章abstract::Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease characterized by progressive lung scarring and excessive extracellular matrix depositon. When stimulated, alveolar epithelial cells (AECs) are aberrantly activated, the expression of profibrotic molecules is enhanced, and lung fibro...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2019.4201
更新日期:2019-07-01 00:00:00
abstract::In recent years, a new cell-based high throughput paradigm has emerged, which seeks to identify novel, pharmacologically active cytoprotective compounds. The essence of this approach is to create experimental models of cell injury relevant for a particular disease by establishing in vitro cell-based models, followed b...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm_00000373
更新日期:2010-04-01 00:00:00
abstract::The human immunodeficiency virus type 1 (HIV-1) epidemic in Brazil is spreading to small municipalities as well as the innermost parts of the country and scarce information has been reported on the frequency of HIV-1 resistance-associated mutations in these areas. To determine the frequency and diversity of the HIV-1 ...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2010-10-01 00:00:00
abstract::Despite recent advances in the management of thyroid cancer, the survival rate of this tumor may still be improved. Therefore, the identification of biological and molecular features of indolent and aggressive disease would be critical to define clinically useful predictors of high-...
journal_title:International journal of molecular medicine
pub_type: 杂志文章,评审
doi:10.3892/ijmm.2012.1089
更新日期:2012-11-01 00:00:00
abstract::Oxidative stress-induced apoptosis is associated with neuronal cell death and ischemia. The NOL3 [nucleolar protein 3 (apoptosis repressor with CARD domain)] protein protects against oxidative stress-induced cell death. However, the protective mechanism responsible for this effect as well as the effects of NOL3 agains...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2016.2596
更新日期:2016-07-01 00:00:00
abstract::To investigate whether in vivo gene transfer causes leptin-antagonistic effects on food intake, animal body weight and fat tissue weight, the R128Q mutated-leptin gene, an R to Q substitution at position 128 of mouse leptin, was transferred into mouse liver and leg muscle by electroporation and hydrodynamics-based gen...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2005-12-01 00:00:00
abstract::We have previously reported that the EVn-50 mixture of vitexins (lignan compounds) containing the purified vitexin (neolignan) compound, 6-hydroxy-4(4-hydroxy-3-methoxyphenyl)-3-hydroxymethyl‑7-methoxy-3,4-dihydro-2-naphthaldehyde, termed VB1, exhibits potent anticancer activity through the induction of apoptosis in s...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2013.1567
更新日期:2014-02-01 00:00:00
abstract::The advanced glycation end‑product (AGE)‑receptor for AGE (RAGE) axis induces transforming growth factor‑β (TGF‑β) expression, cell hypertrophy and increases extracellular matrices that are indicated in the pathogenesis of diabetic nephropathy (DN). RAGE binds to numerous ligands besides AGE, including S100B. In the p...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2014.2024
更新日期:2015-02-01 00:00:00
abstract::The aim of the present study was to examine the protective effect of caveolin‑1 (Cav‑1) in the penehyclidine hydrochloride (PHC)‑based inhibition of lipopolysaccharide (LPS)‑induced acute lung injury (ALI) in vivo and in vitro, in addition to the potential underlying mechanisms. In vivo, an ALI rat model was establish...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2019.4117
更新日期:2019-05-01 00:00:00
abstract::Rats exposed from 7 weeks after birth and for the ensuing 3 to 7 months to a diet depleted in long-chain polyunsaturated omega3 fatty acids were recently proposed as a new animal model for the metabolic syndrome. The present study aimed mainly at investigating whether, in this new model, the perturbation of the fatty ...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2009-08-01 00:00:00
abstract::Graves' ophthalmopathy (GO) is considered to be an organ-specific autoimmune disease. However, the pathogenesis of GO is incompletely understood at the present time. To clarify the immunological differences between newly diagnosed GO and Graves' disease (GD) without ophthalmopathy or healthy controls (HC), we examined...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2006-05-01 00:00:00
abstract::The phospholipase A (PLA)2 family is the most complex gene family of phospholipases and plays a crucial role in a number of physiological activities. However, the phylogenetic background of the PLA2 gene family and the amino acid residues of the PLA2G7 gene following positive selection gene remain undetermined. In thi...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2014.2047
更新日期:2015-03-01 00:00:00
abstract::MicroRNAs (miRNAs or miRs) have emerged as key regulators of gene expression in essential cellular processes, such as cell growth, differentiation and development. Recent findings have established that the levels of miRNAs are modulated by cell signaling mechanisms, including the bone morphogenetic protein (BMP) signa...
journal_title:International journal of molecular medicine
pub_type: 杂志文章,评审
doi:10.3892/ijmm.2015.2060
更新日期:2015-03-01 00:00:00
abstract::This study investigated the effects of mycelial extract and culture filtrate of Cordyceps sphecocephala J201 on airway hyper-responsiveness, pulmonary immune cell infiltration, and Th2 cytokine expression in animal models of asthma. After Concanavalin A (Con A) activation of mouse primary spleen cells, the IL-4 and IL...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2010-09-01 00:00:00
abstract::It has been reported that the degeneration of cochlear hair cells is the typical cause of presbycusis (or age-related hearing loss). However, the molecular mechanisms that mediate cochlear hair cell apoptosis are not yet fully understood and there is no effective treatment for this disorder. MicroRNAs (miRNAs or miRs)...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2016.2735
更新日期:2016-11-01 00:00:00
abstract::Krüppel‑like family (KLF) members are important regulators of proinflammatory activation in the vasculature. A transcriptome study involving RNA sequencing (RNA‑seq) and quantitative PCR (qPCR) was performed to investigate Klf15 and Klf15‑regulated gene levels in C57BL/6 mice with inferior vena cava thrombi and in con...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2020.4538
更新日期:2020-06-01 00:00:00
abstract::The circulating concentrations of triglycerides, high density lipoprotein (HDL)‑cholesterol, and low density lipoprotein (LDL)‑cholesterol have a substantial genetic component, and the heritability of early‑onset dyslipidemia might be expected to be higher compared with late‑onset forms. In the present study, exome‑wi...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2018.3943
更新日期:2019-01-01 00:00:00
abstract::Hepatoblastoma is a rare pediatric liver tumor. While much progress has been made in the treatment of the disease, very little is known about the moleculer events underlying the pathogenesis of this disease. We sought to investigate a series of hepatoblastomas for alterations in gene expression patterns with emphasis ...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2000-08-01 00:00:00
abstract::Subsequently to the publication of this article, the authors have realized that the address affiliation for the corresponding author, Chengheng Hu, and the authors Longyun Peng and Xinxue Liao appeared incorrectly. These authors' affiliation information should have appeared as follows (the corrected address affiliatio...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2018.3708
更新日期:2018-09-01 00:00:00
abstract::Thioredoxin (TRX), which is a stress-inducible protein with redox-active disulfide structures, has various biological activities by regulating DNA binding of transcription factors in cells. In Graves' disease that is among the common diseases of the thyroid, endogenous stresses that are induced by excess thyroid hormo...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2005-05-01 00:00:00
abstract::Xuebijing injection (XBJ) has long been used to treat infectious diseases in China. The therapeutic effect of XBJ is probably associated with anti-inflammatory effects. However, the precise mechanisms responsible for the effects of XBJ remain unknown. The present study was conducted in order to evaluate the protective...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2016.2749
更新日期:2016-11-01 00:00:00
abstract::Elucidation of the molecular mechanisms governing the osteogenic differentiation of human mesenchymal stem cells (hMSCs) is of great importance for improving the treatment of bone-related diseases. MicroRNAs (miRNAs or miRs), a class of small non-coding RNAs, are critical in a number of biological processes, including...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2015.2275
更新日期:2015-09-01 00:00:00
abstract::The underground parts of Nardostachys chinensis (N. chinensis), which belongs the genus Valerianaceae, have been used as sedative and analgesic agents in traditional Korean medicine for centuries. The mitogen-activated protein kinases (MAPKs) are serine/threonine kinases involved in the regulation of various cellular ...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2013.1596
更新日期:2014-03-01 00:00:00
abstract::Although endogenous digitalis‑like factor (EDLF) is associated with the development of various physical disorders, the role in preeclampsia remains unclear. This study investigated the effects of EDLF on vascular endothelial cell damage in patients with preeclampsia and the potential mechanisms. From July 2014 to July...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2017.3316
更新日期:2018-02-01 00:00:00
abstract::Kelch‑like ECH‑associated protein 1 (Keap1)/nuclear factor erythroid 2‑related factor 2 (Nrf2) signaling has a protective effect on normal cells. A number of previous studies demonstrated that Keap1/Nrf2 signaling is associated with drug resistance in numerous tumors. The aim of the present study was to investigate th...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2019.4134
更新日期:2019-05-01 00:00:00
abstract::Tubular atrophy and dysfunction is a critical process underlying diabetic nephropathy (DN). Understanding the mechanisms underlying renal tubular epithelial cell survival is important for the prevention of kidney failure associated with glucotoxicity. Autophagy is a cellular pathway involved in protein and organelle d...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2014.2052
更新日期:2015-03-01 00:00:00
abstract::Effective drugs and strategies for treating type 2 diabetes mellitus (2‑DM) are urgently required. The aim of the present study was to elucidate the mechanism underlying microRNA (miR)‑6835‑3p regulation of adiponectin receptor 1 (AdipoR1) expression and the miR‑6835‑3p/AdipoR1 signaling pathway in pancreatic islet ce...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2018.3731
更新日期:2018-09-01 00:00:00
abstract::The mechanisms through which mechanical ventilation causes non-infectious inflammatory diseases and lung injury are poorly understood. Animals models of this type of injury suggest that it involves signaling mediated by Toll‑like receptor (TLR)4 and 9. In this study, in order to gain further insight into the involveme...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2017.2873
更新日期:2017-03-01 00:00:00
abstract::Triticum aestivum sprout-derived polysaccharide (TASP) has anti-diabetic properties, but no information is available in regards to its protective effect against ethanol-induced hepatic injury. This study aimed to investigate the mechanism behind the protective role of TASP against ethanol-induced liver injury in vivo....
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2017.3095
更新日期:2017-10-01 00:00:00
abstract::Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a key coordinator of gene programs in metabolism and energy homeostasis in mammals. The aim of this study was to determine whether PGC-1α is involved in the transcriptional regulation of retinal neovascularization in oxygen-induced retinopathy (OI...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2014.1717
更新日期:2014-06-01 00:00:00