Airborne particulate matter (PM) is a major health hazard worldwide and is a key factor in lung cancer, which remains the most common type of malignancy and the leading cause of cancer-related deaths. DNA methylation is a critical mechanism underlying the detrimental effects of PM, however, the molecular link between PM exposure and lung cancer remains to be elucidated. N-α-acetyltransferase 10 (NAA10) is involved in the cell cycle, migration, apoptosis, differentiation, and proliferation.
View Article and Find Full Text PDFObjectives: Lung cancer is the leading cause of cancer-related deaths and is currently a major health problem owing to difficulties in diagnosis at the early stage of the disease. Changes in DNA methylation status have now been identified as a critical component in the initiation of lung cancer, and the detection of DNA methylation is expected to be an important method for the early diagnosis of lung cancer. Nicotine, the principal tobacco alkaloid, directly contributes to lung carcinogenesis through the activation of nicotinic acetylcholine receptors (nAchRs).
View Article and Find Full Text PDFLung cancer is a leading cause of cancer-related mortality across the world and tobacco smoking is the major risk factor. The Wnt signaling pathway is known to be involved in smoke-induced tumorigenesis in the lung. Promoter hypermethylation of Wnt inhibitory factor 1 (Wif1) has become a common event in a number of human tumors.
View Article and Find Full Text PDFIntroduction: Liver kinase 1 (LKB1) plays a critical barrier role in lung tumorigenesis by controlling initiation, differentiation and metastasis. We searched for genetic and epigenetic alterations of the LKB1 gene in Korean non-small cell lung cancers (NSCLCs) and correlated the results with clinicopathological features. We also investigated the relationship between genetic and epigenetic alterations of LKB1 and mutations in the TP53 gene and epidermal growth factor receptor (EGFR) pathway genes.
View Article and Find Full Text PDFDickkopf-1 (DKK1) is known as a negative regulator of the Wnt signaling pathway, which plays a crucial role in carcinogenesis. However, aberrant expression and the role of DKK1 in human cancers remain controversial. To estimate the role of DKK1 and its prognostic potential in lung cancer, promoter methylation of DKK1 was evaluated in 139 primary non-small cell lung cancers (NSCLCs) by methylation-specific PCR and its association with clinical and prognostic parameters.
View Article and Find Full Text PDFLung cancer remains a global health problem with a high mortality rate. CpG island methylation is a common aberration frequently associated with gene silencing in multiple tumor types, emerging as a highly promising biomarker. The transmembrane protein with a single EGF-like and two follistatin domains (TMEFF2) is epigenetically silenced in numerous tumor types, suggesting a potential role as a potential tumor suppressor.
View Article and Find Full Text PDFNuclear targeting of bacterial proteins has emerged as a pathogenic mechanism whereby bacterial proteins induce host cell pathology. In this study, we examined nuclear targeting of Acinetobacter baumannii transposase (Tnp) and subsequent epigenetic changes in host cells. Tnp of A.
View Article and Find Full Text PDFLung cancer is the leading cause of cancer-related deaths worldwide and is usually associated with a late diagnosis and a poor prognosis. Thymosin β(10) (TMSB10) is a monomeric actin sequestering protein that regulates actin cytoskeleton organization. The aberrant TMSB10 expression has been implicated in the pathogenesis of human cancers.
View Article and Find Full Text PDFLung cancer is the major health problem and leading cause of cancer-related deaths worldwide owing to late diagnosis and poor prognosis. Aberrant promoter methylation is an important mechanism for silencing tumor-suppressor genes in cancer and a promising tool for the development of molecular biomarkers. Ras association domain family 1A (RASSF1A), a pivotal gatekeeper of cell cycle progression, is highly methylated in a wide range of human sporadic tumors, including lung cancer.
View Article and Find Full Text PDFBackground And Objective: The exact role of the cystic fibrosis transmembrane conductance regulator (CFTR) in pathophysiology, and the mechanisms regulating its expression are poorly understood. The CFTR gene is known to be genetically or epigenetically associated with several cancers. In the present study, the methylation status of the promoter region of the CFTR gene and its expression in primary non-small cell lung cancer (NSCLC) were investigated.
View Article and Find Full Text PDFBackground: Lung cancer is the leading cause of cancer-related deaths worldwide. Epigenetic inactivation of certain genes by aberrant promoter methylation is recognized as a crucial component in the initiation and progression of lung cancer. Response gene to complement 32 (RGC32) has been identified as a cell cycle regulator induced by activation of complements; however, its role in carcinogenesis is still controversial.
View Article and Find Full Text PDFThe growth arrest DNA-damage-inducible protein 45 (GADD45) can serve as a key coordinator of the stress response by regulating cell cycle progression, genomic stability, DNA repair, and other stress-related responses. Although deregulation of GADD45 expression has been reported in several types of human tumors, its role in lung cancer is still unknown. DNA hypermethylation of promoter CpG islands is known to be a major mechanism for epigenetic inactivation of tumor suppressor genes.
View Article and Find Full Text PDFCpG islands (CGIs) hypermethylation is implicated in the pathogenesis of many cancers, including lung cancer. The phosphate and tension homolog (PTEN) is a tumor suppressor that controls a variety of biological processes including cell proliferation, growth, migration, and death. The defects in PTEN regulation have a profound impact on carcinogenesis.
View Article and Find Full Text PDFRetinoid X receptors (RXRs) are nuclear receptors for retinoids that play a critical role in the regulation of growth and differentiation in normal and tumor cells. Deregulation of RXR expression has been reported in non-small cell lung cancer (NSCLC); however, the mechanism underlying the impaired expression of RXRs in lung cancer is not known. Aberrant methylation of promoter CpG islands is known to be a major mechanism for inactivation of tumor suppressor genes.
View Article and Find Full Text PDFObox genes are preferentially expressed in the ovary, testis and oocyte, and play important roles in many developmental processes. In this study, we report that Obox4 and Obox6 are expressed in mouse embryonic stem cells (mESCs) and that Obox4 regulates histone family gene expression in mESCs. Obox4 protein expressing mESCs formed colonies with a flattened and irregular morphology, and exhibited decreased expression levels of self-renewal related proteins, such as Oct4 and Sox2, as well as reduced alkaline phosphatase activity.
View Article and Find Full Text PDFNuclear targeting of bacterial proteins is an emerging pathogenic mechanism whereby bacterial proteins can interact with nuclear molecules and alter the physiology of host cells. The fully sequenced bacterial genome can predict proteins that target the nuclei of host cells based on the presence of nuclear localization signal (NLS). In the present study, we predicted bacterial proteins with the NLS sequences from Klebsiella pneumoniae by bioinformatic analysis, and 13 proteins were identified as carrying putative NLS sequences.
View Article and Find Full Text PDFPromoter methylation is an important mechanism in gene silencing and is a key epigenetic event in cancer development. Homeobox A5 (HOXA5) is a master regulator of the morphogenesis and cell differentiation to be implicated as a tumor suppressor gene in breast cancer, but its role in lung cancer is still unknown. In this study, we have investigated the methylation status of the promoter region of the HOXA5 gene in nonsmall cell lung cancers (NSCLCs) using nested and standard methylation-specific PCR (MSP) and correlated the methylation status with clinicopathological features.
View Article and Find Full Text PDFLung cancer is the leading cause of cancer deaths worldwide and is usually associated with late diagnosis and poor prognosis. Tumor-acquired methylation of the promoter CpG islands (CGIs) is an important mechanism for silencing tumor suppressor genes. The checkpoint kinase 2 (CHK2) is a tumor suppressor that plays a crucial role in regulating cell-cycle checkpoints and apoptosis following DNA damage.
View Article and Find Full Text PDFTo examine whether the epigenetic status of the human Oct4 promoter is similarly regulated in mouse cells, we engineered a human bacterial artificial chromosome to express green fluorescent protein under the control of the hOct4 promoter and stably integrated it into mouse embryonic stem cells (mESCs), NIH3T3, and 293T cells. The hOct4 promoter is unmethylated in mESCs and it undergoes methylation during retinoic acid-induced differentiation. However, the hOct4 promoter is demethylated in NIH3T3 cells even though it is fully methylated in 293T cells.
View Article and Find Full Text PDFThe tumor suppressor gene Ras association domain family 1A (RASSF1A) is highly methylated in a wide range of human sporadic tumors. The current study investigated the hypermethylation of RASSF1A, the expression of RASSF1A protein, and the correlation between these and the clinicopathological features of gallbladder (GB) cancer in Korean patients. Formalin-fixed, paraffin-embedded tumors and non-neoplastic GB tissues (22 carcinomas, 8 adenomas, 26 normal epithelia) were collected from patients who had undergone surgical resection.
View Article and Find Full Text PDFSquamous cell carcinoma of the head and neck (SCCHN) is a relatively rare cancer with a poor prognosis. In the present study, we investigated susceptibility biomarkers for SCCHN in 155 Koreans (73 SCCHN cases and 82 controls). Expression of the xeroderma pigmentosum group C (XPC) DNA-repair gene was measured by TaqMan fluorogenic real-time RT-PCR using RNA isolated from peripheral blood samples.
View Article and Find Full Text PDFUrinary 1-hydroxypyrene (1-OHP), an exposure biomarker for polycyclic aromatic hydrocarbons (PAHs), was used to identify potential sources of PAH exposure for 660 Koreans who were not occupationally exposed to PAHs (65% male; 35% female; mean age, 36.5 +/- 11.1 years).
View Article and Find Full Text PDFUrinary 1-hydroxypyrene (1-OHP) has been used as a biomarker for assessing the level of exposure to environmental carcinogenic polycyclic aromatic hydrocarbons (PAHs). In order to perform the appropriate biological monitoring for examining the level of exposure to PAHs, this study investigated whether or not genetic polymorphisms of the metabolic enzymes, which might be involved in the metabolism of pyrene, affected the urinary 1-OHP levels in a population of 661 Koreans (male, 63%; female, 37%; mean age, 36.5 +/- 11.
View Article and Find Full Text PDFTo conduct proper biological monitoring of environmental exposure to bisphenol A (BPA), the variation in host susceptibility need to be investigated. For this purpose, we studied effects of genetic polymorphism in sulfotransferase (SULT) 1A1 on urinary BPA, a biomarker for BPA exposure, in 73 Koreans (male, 34; female, 39; age, 48.9 +/- 11.
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