ObjectiveRecent advancements in the researches on cholangiocarcinoma (CC) related genes methylation in CC were reviewed and the clinical significances of aberrant DNA methylation for the diagnosis and treatment of CC were discussed. MethodsRelevant literatures about the relation between CC-related genes methylation and CC published recently were collected and reviewed. ResultsThe genesis of CC resulted from abnormal expressions of many genes. Many researches had shown that the abnormal methylation of CC-related genes had a close relation with CC. Epigenetic alteration had been acknowledged as an important mechanism contributing to early CC carcinogenesis. ConclusionsAbnormal methylation of CC-related genes is related with CC. The detection of CC-related genes methylation might provide new specific biomarkers for early noninvasive diagnosis of this disease. Using epigenetic agents such as azacytidine to modulate the activities of DNA methyltransferase and reverse the methylation status of CC-related gene might be an attractive strategy for future treatment of CC, which could be combined with conventional therapies.
ObjectiveTo investigate the difference of DNA methylation before and after bariatric surgery.MethodThe relevant literatures of the research on the changes of DNA methylation level and gene expression regulation in blood and tissues before and after bariatric surgery were retrieved and reviewed.ResultsDNA methylation was an important method of epigenetic regulation in organisms and its role in bariatric surgery had been paid more and more attention in recent years. Existing studies had found that there were changes of DNA methylation in blood and tissues before and after bariatric surgery. The degree of methylation varies with different follow-up time after bariatric surgery and the same gene had different degrees of methylation in different tissues, and some even had the opposite results.ConclusionsDNA methylation levels before and after bariatric surgery are different in different tissues. And studies with larger sample size and longer follow-up time are needed, to further reveal relationship among DNA methylation, obesity, and bariatric surgery.
Objective To investigate the effects of DNA methyltransferase inhibitor (DNMTi) and histone deacetylase inhibitor (HDCAi) on expression of E-cadherin gene and invasiveness of cholangiocarcinoma cell. Methods According to different treatment, the QBC939 cells were divided into four groups: blank control group, hydralazine group, valproic acid group and hydralazine and valproic acid combined group. After 48 h, the expression of E-cadherin was evaluated by reverse transcription-PCR (RT-PCR), mehtylation specific PCR (MSP) and Western blot, the invasiveness of QBC939 cells was evaluated by Transwell method. Results There was no expression of E-cadherin mRNA and protien in blank control group and valproic acid group. The expressions of E-cadherin mRNA and protien in hydralazine and valproic acid combined group were higher than those in hydralazine group ( P ＜ 0.01), while the invasiveness of QBC939 cells of hydralazine and valproic acid combined group was much lower than that of blank control group, hydralazine group and valproic acid group ( P ＜ 0.01). Conclusion DNMTi and HDACi can synergistically re-express E-cadherin gene and weaken the invasiveness of QBC939 cell, which plays an important part in treatment of cholangiocarcinoma.
ObjectiveTo explore the relationship between aberrant promoter CpG islands methylation status of E-cadherin gene and hepatocarcinogenesis, and to assess its significance in clinical early diagnosis of hepatocellular carcinoma (HCC). MethodsSurgically resected specimens, among which cancerous and corresponding noncancerous liver tissues from 34 HCC patients, 10 liver cirrhosis from patients without HCC and normal liver tissues from 4 accidental deaths, were collected in West China Hospital. Breast cancer cell line MDA-MB-435 with promoter CpG islands hypermethylation of E-cadherin as positive control was gained from the Cell Bank of Chinese Academy of Sciences in Shanghai. The methylation status of promoter CpG island of E-cadherin gene was detected by nested methylationspecific polymerase chain reaction (nested-MSP). ResultsE-cadherin gene promoter CpG islands hypermethylation was found in 61.76% (21/34) of cancerous tissues, in 29.41% (10/34) of noncancereous tissues from the 34 HCC patients and in 50.00% (5/10) liver cirrhosis from patients without HCC. None of the 4 normal liver samples were detected E-cadherin mehylation positive. Moreover, the methylation of E-cadherin gene was significantly more frequent in 34 cancerous than that in corresponding noncancerous liver tissues (Plt;0.05), which had no significant difference between the 10 cirrhotic samples and cancerous or non-cancerous liver tissues (Pgt;0.05). In 34 cancerous samples, with the combination of both biomarkers of E-cadherin methylation and AFP400 (serum AFP level at a cutoff of 400 μg/L), the diagnostic sensitivity of HCC increased to 82.35%. ConclusionsThe aberrant promoter methylation of E-cadherin gene may play a vital role in the development and progression of HCC. Moreover, it might be an early event in hepatocarcinogensis. It is of high value to make further study to confirm the significance of E-cadherin gene methylation in clinical diagnosis and therapy.
The regulation of epigenetics on bone marrow mesenchymal stem cells (BMSCs) has been a research hot spot in medical area. This paper mainly summarizes the progress of the regulation of DNA methylation, histone acetylation, small interfering RNA (siRNA) induced gene silence and microRNA (miRNA) on BMSCs. Our analysis shows that the regulation of epigenetics on BMSCs plays a significant role in the repair of bone tissue, nervous tissue and cardiac muscle.
Objective To identify the N6-methyladenosine (m6A)-related characteristic genes analyzed by gene clustering and immune cell infiltration in myocardial ischemia-reperfusion injury (MI/RI) after cardiopulmonary bypass through machine learning. Methods The differential genes associated with m6A methylation were screened by the dataset GSE132176 in GEO, the samples of the dataset were clustered based on the differential gene expression profile, and the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the differential genes of the m6A cluster after clustering were performed to determine the gene function of the m6A cluster. R software was used to determine the better models in machine learning of support vector machine (SVM) model and random forest (RF) model, which were used to screen m6A-related characteristic genes in MI/RI, and construct characteristic gene nomogram to predict the incidence of disease. R software was used to analyze the correlation between characteristic genes and immune cells, and the online website was used to build a characteristic gene regulatory network. Results In this dataset, a total of 5 m6A-related differential genes were screened, and the gene expression profiles were divided into two clusters for cluster analysis. The enrichment analysis of m6A clusters showed that these genes were mainly involved in regulating monocytes differentiation, response to lipopolysaccharides, response to bacteria-derived molecules, cellular response to decreased oxygen levels, DNA transcription factor binding, DNA-binding transcription activator activity, RNA polymerase Ⅱ specificity, NOD-like receptor signaling pathway, fluid shear stress and atherosclerosis, tumor necrosis factor signaling pathway, interleukin-17 signaling pathway. The RF model was determined by R software as the better model, which determined that METTL3, YTHDF1, RBM15B and METTL14 were characteristic genes of MI/RI, and mast cells, type 1 helper lymphocytes (Th1), type 17 helper lymphocytes (Th17), and macrophages were found to be associated with MI/RI after cardiopulmonary bypass in immune cell infiltration. Conclusion The four characteristic genes METTL3, YTHDF1, RBM15B and METTL14 are obtained by machine learning, while cluster analysis and immune cell infiltration analysis can better reveal the pathophysiological process of MI/RI.
Pulmonary arterial hypertension (PAH) is a fatal and complex disease characterized by multifactorial involvement in pulmonary vascular remodeling, leading to heart failure. It is difficult to treat and has a poor long-term prognosis. Recent studies highlight the significant role of epigenetic modulation in the pathophysiological progression of PAH, offering new therapeutic approaches to improve clinical outcomes. This article summarizes the role of epigenetic modulation in the development and progression of PAH, focusing on deoxyribonucleic acid methylation, ribonucleic acid methylation, histone modifications, and non-coding ribonucleic acid, in order to understand the role of epigenetic modulation in PAH and identifying new evaluation indexes and therapeutic targets, thereby improving the prognosis of PAH.
Objective To investigate the role of DNA methylation on regulation of cell apoptosis and proliferation in ischemia-reperfusion of small intestine. Methods Thirty-five male Wistar rats were randomly divided into normal group， sham operation group， and ischemia-reperfusion group. The apoptotic cell was assessed by TUNEL and electron microscopy and the expression of Ki-67 was examined by immunohistochemistry in the small intestinal parts （villi epithe-lium， crypt epithelium， and lamina propria mucosa of small intestine）. The DNA methylation was detected by DNA histo-endonuclease-linked detection of methylated DNA sites. Results ①The apoptotic positive cells increased at 3 h， 6 h，and 12 h after ischemia-reperfusion in the villi epithelium， crypt epithelium， and lamina propria mucosa of small intestine as compared with the normal group and sham operation group （P＜0.01）；Moreover， the apoptotic cells in the lamina propria mucosa of small intestine were identified as T cells by electron microscopy. ②The expressions of Ki-67 markedly increased at 3 h， 6 h， 12 h， and 24 h after ischemia-reperfusion in the villi epithelium cells as compared with the normal group and sham operation group （P＜0.01）. ③The weak expression of DNA methylation was found in the villi epith-elium and crypt epithelium in the normal group and sham operation group， the b expression was examined in the crypt epithelium cells nearby stem cell site in the ischemia-reperfusion of small intestine， the change of expression was gradually weak from crypt epithelium to villi epithelium. Conclusion This initial results indicate that the DNA methyl-ation in the ischemia-reperfusion of small intestine might regulate cell apoptosis and proliferation.
ObjectiveTo observe the expression and transcription of MART-1 in human uveal melanoma cell lines 92-1, 92-2, Ocm3, Me1285, as well as the possible effect of methylation on its expression.MethodsThe cell lines 92-1, 92-2, Ocm3 and Mel285 were cultured routinely and tested for MART-1 expression at protein and mRNA level by FACS analysis, Western blot and RT-PCR respectively. Methylation status of the MART-1 promoter region in all the cell lines were checked by Southern blots of DNA digested with methylation sensitive restriction enzymes.ResultsAs observed in FACS analysis and Western blot, 92-1, 92-2 and Ocm3 were MART-1 positive cell lines while Me1285 was negative cell line. Consistent with protein analysis, 92-1 and Ocm3 cell lines showed MART-1 specific PCR products and there was no product in Me1285 cell line in RT-PCR. The MART-1 positive cell lines, 92-1, 92-2, and Ocm3 show methylation at the MspI/HpaⅡ site, and the NruⅠ sites of all positive cell lines are not methylated. The MART-1 negative cell line Mel285 shows hypermethylation at the NruⅠsite and the MspⅠ/HpaⅡ site is not methylated.ConclusionsMART-1 could be expressed in human uveal melanoma cell lines 92-1, 92-2 and Ocm3. The change of methylation status of MART-1 promoter may correlate with the transcription of MART-1.