Objective
To investigate the tumor suppressor genes of phlegm DNA in smokers, and analyze the correlation between methylation level of tumor suppressor gene promoter and chronic mucus hypersecretion (CMH).
Methods
The study recruited the patients who were admitted in the respiratory department during 2013-2016 in this hospital, including 700 cases of urban smokers and 380 cases of rural smokers. Eleven genes commonly silenced by promoter methylation in lung cancer and associated with cancer risk were selected. Methylation specific PCR (MSP) was used in the sputum sample of 700 individuals in the urban smokers cohort. Replication was performed in 380 individuals from the rural smokers cohort.
Results
CMH was significantly associated with an overall increased number of methylated genes, with SULF2 methylation demonstrating the most consistent association. The association between SULF2 methylation and CMH was significantly increased in males but not in females both in the urban and rural groups (OR=2.73, 95%CI 1.53-4.93, P=0.001; OR=2.96, 95%CI 1.47-5.94, P=0.002, respectively). Furthermore, the association between methylation and CMH was more obvious among 139 male former smokers with persistent CMH compared with current smokers (SULF2, OR=3.64, 95%CI 1.57-8.35, P=0.002).
Conclusion
These findings demonstrate that especially male former smokers with persistent CMH have markedly increased promoter methylation of lung cancer risk genes and potentially could be at increased risk for lung cancer.
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.
Retinoblastoma (RB) is a common intraocular tumor in children, often leading to blindness or disability, and its pathogenesis involves genetic and epigenetic regulation. Epigenetics regulates gene expression through mechanisms such as DNA methylation and histone modification without altering the DNA sequence, and the imbalance of its homeostasis is considered a crucial factor in the development and progression of RB. Therapeutic strategies targeting these abnormal modifications offer new potential treatment avenues for RB. Although current research has highlighted the importance of epigenetics in RB, the specific mechanisms of action, the relationship with genetic bases, and the development of targeted drugs remain largely unknown. Therefore, further in-depth research into the epigenetic mechanisms of RB is of great significance for elucidating its carcinogenic mechanisms, identifying effective therapeutic targets, and developing new drugs.
ObjectiveTo summarize mechanism of DNA methylation and histone methylation in liver fibrosis.MethodThe literatures on the DNA methylation and histone methylation during the liver fibrosis were reviewed and analyzed.ResultsThe DNA methylation and histone methylation were the important components of epigenetics. The up-regulation or down-regulation of genes during the liver fibrosis leaded to the activation or inactivation of the subsequent pathways. For example, the PTEN, SEPT9, Smad7, etc. were hypermethylated and the expressions were decreased in the liver fibrosis. The Spp1 was hypomethylated and the expression was increased in the liver fibrosis.ConclusionsMethylation affects expression of genes by altering epigenetics of genes. Systematic and in-depth study of role and mechanism of methylation in liver diseases provides a new direction and locations for some target treatments for liver disease.
Objective To evaluate the value of methylated Septin9 (mSEPT9) in the diagnosis and postoperative recurrence/metastasis monitoring of colorectal cancer. Methods A total of 76 patients with colorectal cancer who were hospitalized in Beijing Anorectal Hospital (Beijing Erlonglu Hospital) and positive for mSEPT9 before operation from January to December in 2020 were collected. Nineteen patients who were still positive for mSEPT9 at one week after operation were selected as the msept9 positive group, and 57 patients whose mSEPT9 became negative were selected as the msept9 negative group. The clinicopathological features and postoperative recurrence and metastasis of the two groups were analyzed and compared. Results There were significant differences in lymph node metastasis rate, vascular or nerve infiltration and clinical staging between the mSEPT9 positive group and the mSEPT9 negative group (P=0.024, P=0.009, P=0.009). There was no significant difference in age, gender, tumor location, degree of tumor differentiation, and tumor invasion depth (T stage), P>0.05. Two patients in the mSEPT9 positive group had liver metastases after operation, and there were no cases of metastasis or recurrence in the mSEPT9 negative group (P=0.024). Conclusion The mSEPT9 can be used as a potential tumor marker for the diagnosis of colorectal cancer and the monitoring of postoperative treatment effect, and more attention should be paid to patients who are still positive for mSEPT9 after surgery.
Recent advances in epigenetics indicate that several epigenetic modifications, including acetylation, methylatio, and microRNA (miRNA), play an important role in the pathogenesis of acute kidney injury (AKI). Our study reveales that enhancement of protein acetylation by pharmacological inhibition of class I histone deacetylases leads to more severe tubular injury, and delays the restoration of renal structure and function. The changes in promoter DNA methylation occurs in the kidney with ischemia/reperfusion. MiRNA expression is associated with the regulation of both renal injury and regeneration after AKI. Targeting the epigenetic process may provide a therapeutic treatment for patients with AKI. The purpose of this review is to summarize recent advances in epigenetic regulation of AKI and provide mechanistic insight into the role of acetylation, methylation, and miRNA expression in the pathological processes of AKI.
Objective To review the research progress in relationship between hereditary diffuse gastric cancer (HDGC) and CDH1 gene. Methods Literatures on HDGC which were published in recent years were collected and analyzed. Results Aberrant CDH1 gene is significantly correlated with HDGC: mutations of CDH1 exons play the most important role in pathogenesis of HDGC. Screening CDH1 gene mutation is useful for diagnosis of HDGC as well as the treatments. Alterations of CDH1 other than exon mutation, such as intron mutation, gene promoter methylation and single nucleotide polymorphism may result in downregulation of the gene expression. Further study should be done to confirm the roles of these alterations. Conclusions Alterations of CDH1 gene are significantly associated with the pathogenesis of HDGC. Detecting alterations of CDH1 gene are important for diagnosis and management of HDGC as well as to get insights of the pathogenesis of the disease.
Objective To investigate the possible mechanism of arsenic trioxide (As2O3) inducing P16 gene demethylation and transcription regulation in the retinoblastoma (RB) Cell Line Y79． Methods The induced growth inhibition of Y79 cell was assayed by MTT; The DNA content of Y79 cell was analyzed by flow cytometry after being exposed to As2O3; the methylation status of the P16 gene in Y79 cell line before and after treatment with As2O3 was detected by the nestedmethylation specific PCR and DNA sequencing; the mRNA of P16,DNA methyltransferases (DNMT3A and 3B)gene were determined by RT-PCR． Results As2O3 was able to inhibit the growth of Y79 cell and increase the cell number in G0-G1 phase；P16 gene was not expressed in Y79 cell line and As2O3 can induce itrsquo;s mRNA expression；after 48 hour disposal of As2O3，the methylation levelof P16 gene was apparently attenuated in Y79 cell line,the expression of DNMT3A and DNMT3B was obviously down-regulated． Conclusions P16 gene is the hypermethylation in the retinoblastoma cell line Y79, and As2O3 can inhibite the methylation of P16 gene and upregulate the expression of p16 gene mRNA which inhibits the proliferation of Y79 cell by inducing the G0-G1 arrest, by inhibiting the expression of DNA methyltransferases.
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.
