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1.
Braz. arch. biol. technol ; 65: e22210115, 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1364466

ABSTRACT

Abstract: It has learned that soybean is being affected by a floral disorder known as floral malady where plants fail to develop pod and do notattendfull maturity. For this floral disorder, we present a new methylation-sensitive amplified polymorphism (MSAP) approach for the evaluation of relative quantitative characteristics of non-methylation, hyper-methylation, hemi-methylation, and full methylation status of CCGG sequences, which are recognized by the isoschizomers HpaII and MspI. We applied a technique to analyze alterations in the cytosine methylation a popular Indian soybean (Glycine max L.) genotype, JS-335.The result revealed that in the symptomatic plant, out of 392 MSAP sites, 281 (71.68%), 33 (8.41%),38 (9.69%), and 40(10.20%) found to beun-methylated, hemi-methylated, fully methylated and hyper-methylated, respectively. Whereas, the MSAP profile of asymptomatic plants revealedout of 402MSAP sites, 330 (81.28%) was un-methylated, 22(5.41%) hemi-methylated,29(7.14%) fully methylatedand 25 (6.15%) hypermethylated. In comparison with asymptomatic(18.71%) plant, approximately 10% increased methylation was noted in symptomatic(28.31%) plantprofiles. The increased levels of methylation was recorded in the symptomatic plants about 28.31%and18.71% in asymptomatic. The study showed a higher epigenetic influence on JS-335 genotype of floral malady symptomatic than same genotype of asymptomatic plant. No pod formation in symptomatic plant induce genome wide changes either in promoter or coding region of gene(s) and DNA fragments showing polymorphism related to differences in pattern and extent of methylation associated with floral malady.

2.
Rev. colomb. reumatol ; 28(supl.1): 31-38, Dec. 2021.
Article in English | LILACS-Express | LILACS | ID: biblio-1360999

ABSTRACT

ABSTRACT The heterogeneity of SLE is a major limitation when designing clinical trials and understand ing the mechanisms of the disease. The analyses conducted before the new technologies for the identification of the single cell transcriptome focused on the detection of molecular patterns such as interferon signature in total blood or through the analysis of major sepa rate cell populations, such as CD4+ T cells. The analyses of molecular patterns have mainly focused on the transcriptome and DNA methylation changes. The first studies on single cell transcriptomics have now been published for mononuclear blood cells and tissues or the knowledge derived from them, total kidney, tubules and skin keratinocytes. The latter have defined patterns of nonresponse to treatment. However, much work still needs to be done to be able to use these methods in clinical practice.


RESUMEN La heterogeneidad del lupus es una limitante al momento de diseñar estudios clínicos, así como también para nuestra facultad de comprender los mecanismos de la enfermedad. Los análisis previos a las nuevas tecnologías para la detección del transcriptoma de célula única trabajaron en la identificación de patrones moleculares, como la firma del interferón en sangre total, o a través del análisis de poblaciones celulares principales separadas, como son las células T CD4+. Los análisis de patrones moleculares se han enfocado primordialmente en el transcriptoma y en los cambios de metilación del ADN. Ya se han publicado los primeros estudios de transcriptoma de célula única para células sanguíneas mononucleares y para tejidos, riñón total, túbulos y queratinocitos de piel. Estos últimos han definido patrones de no-respuesta al tratamiento. Aún falta mucho para que los métodos o los conocimientos derivados de los mismos sean de utilidad en la práctica clínica.

3.
Arq. gastroenterol ; 58(1): 55-60, Jan.-Mar. 2021. tab, graf
Article in English | LILACS | ID: biblio-1248983

ABSTRACT

ABSTRACT BACKGROUND: Colorectal cancer is the third most common neoplasm in the world. Methylation of tumor related genes in CpG islands can cause gene silencing and been involved in the development of cancer. The potential role of DKK2 as a biomarker for early diagnosis of colorectal cancer remains unclear. OBJECTIVE: The aim of the study was to evaluate the profile of methylation and RNAm expression of DKK2 as potential predictors of colorectal cancer diagnosis and prognosis. METHODS: Expression of mRNAs encoding DKK2 in 35 colorectal cancer tissues was quantified using real-time polymerase chain reaction analysis. The DNA methylation was studied by high resolution melting analysis. The general characteristics of the patients were collected. DKK2 methylation and expression were compared to clinical, pathological aspects and overall survival. RESULTS: Among the 35 patients studied, 18 were male, 10 were on right colon and 25 on left colon. Among the 20 patients with high hypermethylation, 15 of them had mRNA low expression of DKK2. There was no significant association between DKK2 promoter methylation and mRNA DKK2 expression and clinical or pathological features. DKK2 promoter methylation (P=0.154) and DKK2 RNA expression (P=0.345) did not show significant correlation with overall survival. CONCLUSION: DKK2 promoter methylation and DKK2 RNA status appear to be biomarkers of cancer diagnosis but not predictors of prognosis.


RESUMO CONTEXTO: O câncer colorretal é a terceira neoplasia mais comum no mundo. A metilação de alguns genes nas ilhas CpG podem causar silenciamento gênico e estar envolvida no desenvolvimento de câncer. O potencial papel de DKK2 como um biomarcador no diagnóstico precoce de CCR permanece incerto. OBJETIVO: O objetivo do estudo foi avaliar o perfil de metilação e expressão de RNAm do gene DKK2 para identificar preditores potenciais de diagnóstico e prognóstico de CCR. MÉTODOS: A expressão de mRNAs que codificam DKK2 em 35 tecidos de câncer colorretal foi quantificada por reação em cadeia da polimerase em tempo real e a metilação do DNA foi verificada por análise de alta resolução. As características gerais dos pacientes foram coletadas. A metilação e expressão de DKK2 foram comparadas aos aspectos clínicos, patológicos e à sobrevida global. RESULTADOS: Entre os 35 pacientes estudados, 18 eram do sexo masculino, 10 tumores eram do cólon ascendente ou transverso e 25 do descendente ou reto. Entre os 20 pacientes com hipermetilação, 12 deles apresentaram baixa expressão de RNAm do gene DKK2. Não houve associação significativa entre a metilação do promotor de DKK2 e a expressão de RNAm de DKK2 e características clínicas ou patológicas. A metilação do promotor de DKK2 e a expressão do RNA de DKK2 não mostraram correlação com sobrevida global dos pacientes com CCR. CONCLUSÃO: A metilação do gene promotor e a expressão do RNAm do gene DKK2 parecem ser biomarcadores de diagnóstico de câncer, mas não se mostraram úteis na avaliação prognóstica.


Subject(s)
Humans , Male , Female , Colorectal Neoplasms/genetics , DNA Methylation , Prognosis , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Promoter Regions, Genetic , CpG Islands , Intercellular Signaling Peptides and Proteins/genetics
4.
Article in Chinese | WPRIM | ID: wpr-907783

ABSTRACT

Objective:To detect the methylation level and mRNA expression level of peroxisome proliferator activated receptory-coactivator-1α (PGC-1α) gene in placental tissue of pregnant women with gestational diabetes (GDM) and to explore the relationship between them and fetal distress.Methods:A total of 174 pregnant women with GDM admitted to in our hospital from Jul. 2018 to Dec. 2019 were selected as the study objects, among which 78 pregnant women with fetal distress were selected as the fetal distress group; and 96 pregnant women with normal delivery and without fetal distress were the control group; during the same period, 82 normal pregnant women without GDM were selected as the healthy group. The methylation level of PGC-1α gene in placenta was detected by direct sequencing after DNA was treated with sodium bisulfite; the expression of PGC-1α mRNA in placenta was detected by real-time fluorescence quantitative PCR (qRT-PCR) ; the levels of triglyceride (TG) , total cholesterol (TC) , low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) were measured by automatic biochemical analyzer; the relationship between methylation frequency of PGC-1α gene and the expression level of PGC-1α mRNA was analyzed; and the influencing factors of fetal distress were analyzed.Results:PGC-1α gene methylation frequency and TG level were higher in the fetal distress group [ (25.42±7.31) %, (4.72±0.68) mmol/L] than in the control group [ (9.26±2.67) %, (4.31±0.64) mmol/L] and the healthy group [ (3.24±1.07) %, (4.33±0.72) mmol/L]. PGC-1α gene methylation frequency was higher in the control group than in the healthy group, and the differences were statistically significant ( P<0.05) ; PGC-1α mRNA expression level in fetal distress group (0.67±0.16) is lower than that in the control group (0.74±0.14) and healthy group (1.00±0.27) . PGC-1α mRNA expression level in control group was lower than that in healthy group, and the difference was statistically significant ( P<0.05) ; the methylation frequency of PGC-1α gene was negatively correlated with the expression level of PGC-1α mRNA in pregnant women with fetal distress ( r=-0.515, P<0.05) ; the methylation of PGC-1α gene was an independent risk factor for fetal distress ( P<0.05) , and the high expression of PGC-1α mRNA was the protective factor of fetal distress ( P<0.05) . Conclusion:DNA methylation level of PGC-1α gene in pregnant women with GDM is related to fetal distress, which may be the target of gene modification for fetal distress.

5.
Chinese Journal of Digestion ; (12): 546-553, 2021.
Article in Chinese | WPRIM | ID: wpr-912210

ABSTRACT

Objective:To investigate the expression, regulation, potential mechanism and clinical significance of microRNA(miRNA)-129-1 in colon cancer.Methods:The changes of expression and methylation of miRNA-129-1 were analyzed from the methylation, mRNA expression and miRNA expression data of colon cancer in the cancer genome atlas (TCGA) database. The target genes of miRNA-129-1 were predicted from miRwalk 2.0 and TargetScan database. DAVID 6.7 online software was used for gene oncology and Kyoto encyclopedia of genes and genomes enrichment analysis. STRING database was used for protein-protein interaction analysis. TCGA data were applied again to analyze the differential expression and prognosis of key target genes of miRNA-129-1. Paired t test and independent sample t test were used for statistical analysis. The receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of miRNA-129-1 gene methylation in colon cancer. Kaplan-Meier method and log-rank test were used to analyze the effects of miRNA-129-1 expression on survival. Results:The sequence of miRNA-129-1 among different species was conserved. After all colon cancer samples, and control samples of TCGA database were analyzed, the results showed that compared with those of control samples, the expression of miRNA-129-1 decreased in cancer samples (0.98±0.81 vs. 5.74±0.59), and the methylation levels of cg04524088, cg04840800, cg11364290, cg20734982 and cg24044186 locus of miRNA-129-1 significantly decreased (0.321±0.130 vs. 0.563±0.051, 0.432±0.123 vs. 0.624±0.064, 0.475±0.153 vs. 0.768±0.033, 0.659±0.180 vs. 0.816±0.037 and 0.862±0.096 vs. 0.916±0.019, respectively) in colon cancer tissues, and the differences were all statistically significant ( t=14.95, 11.36, 9.39, 11.74, 5.32 and 3.47, all P<0.01). The results of ROC analysis showed that the methylation levels of the above five locus of miRNA-129-1 gene had high diagnostic efficiency in colon cancer (area under curve=0.946, 0.915, 0.950, 0.758 and 0.667, all P<0.01). The results of survival analysis indicated that low expression of miRNA-129-1 was associated with poor prognosis (hazard ratio ( HR)=0.55, P=0.018). The results of bioinformatics analysis demonstrated that the target genes of miRNA-129-1 were enriched in serine / threonine kinase receptor, mitogen-activated protein kinase and other functional gene clusters closely related to tumor, and there was a complex interaction network among the target genes proteins. The high expression of ephrin type-B receptor2 ( EPHB2) gene, a potential key target gene of miRNA-129-1, was associated with the short overall survival and disease-free survival time ( HR=1.9 and 1.6, both P<0.01). Conclusions:The expression and methylation of miRNA-129-1 play an important regulatory role in the development and development of colon cancer. The methylation of miRNA-129-1 has potential value in the diagnosis of colon cancer, and miRNA-129-1 is an influencing factor for the prognosis of patients with colon cancer. EPHB2 may be a potential key target gene of miRNA-129-1.

6.
Chinese Journal of Neurology ; (12): 1119-1127, 2021.
Article in Chinese | WPRIM | ID: wpr-911845

ABSTRACT

Objective:To preliminarily explore the association between single nucleotide polymorphisms (SNP) of five candidate genes (APH1B, PRNP, HMGCR, SIRT1, ApoE) and Alzheimer′s disease (AD), and to analyze the methylation levels of BAX and ApoE promoters on the pathogenesis of AD.Methods:Seventeen cases who were admitted to the Department of Geriatrics of the First Affiliated Hospital of Xinjiang Medical University from 2014 to 2015 and diagnosed as likely to be AD by geriatrician and neurologists according to the AD diagnostic criteria in 4th Revised Edition of the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association served AD group, with an age of (75.65±5.86) years, and 34 non-AD patients with matching baseline data such as age, gender, ethnicity, and education status among patients hospitalized during the same period were selected as control group, with an age of (77.59±7.41) years. Sanger sequencing method was used for SNP typing of candidate genes. Methylation-specific polymerase chain reaction was used to determine the DNA methylation level.Results:The distribution of ApoE ε4 allele was statistically different between the AD group and the control group (χ 2=9.718, P=0.002). Candidate genes (SIRT1 rs7895833, APH1B rs1047552, PRNP rs1799990, HMGCR rs3846662) SNP locus genotypes and alleles had no statistically significant differences in the distribution between the AD group and the control group ( P>0.05). After stratification according to whether they carried ApoE ε4, no statistically significant difference was found between the two groups ( P>0.05). The BAX promoter methylation level of the AD group (0.045±0.025) was lower than that of the control group (0.061±0.028) ( t=-2.078, P=0.045). After gender stratification, the BAX methylation level of the female AD group (0.044±0.021) was lower than that of the control group (0.065±0.275) ( t=-2.230, P=0.045). There was no statistically significant difference in the methylation level of ApoE promoter between the AD group and the control group ( P>0.05). After stratification according to whether they carry ApoE ε4 or not, the methylation level of AD patients with ApoE ε4 allele (1.553±0.291) was higher than that of non-carriers (1.221±0.261) ( t=2.480, P=0.025). Conclusions:ApoE ε4 allele may be a risk factor for the onset of AD. BAX promoter hypomethylation contributes to AD in the elderly in Xinjiang, especially in female. ApoE ε4 allele may cause AD through the interaction with ApoE methylation.

7.
Chinese Journal of Dermatology ; (12): 966-972, 2021.
Article in Chinese | WPRIM | ID: wpr-911555

ABSTRACT

Objective:To screen aberrant DNA methylation sites associated with melanoma using gene chip technology, and to preliminarily construct a melanoma-specific methylation profile.Methods:The Illumina Human Methylation 450K whole-genome methylation chip was used to detect the whole-genome DNA in 6 melanoma tissues and their paralesional skin tissues, and DNA differentially methylated sites were obtained. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) -based pathway analysis were carried out to investigate gene functions.Results:Gene chip testing showed that there were 27 779 differentially methylated sites between melanoma tissues and paralesional tissues, of which 16 673 were hypermethylated sites and 11 106 were hypomethylated sites in melanoma tissues. According to more stringent screening criteria " P < 0.01 and |Δβ| > 0.2", a total of 4 883 differentially methylated sites were screened out after filtering out all single nucleotide polymorphism-related probes, probes located on the XY chromosomes and cross-reactive probes, 1 459 (30%) of which were located in the promoter region including TSS1500, TSS200, 5′UTR and 1st Exon. GO enrichment analysis showed that differentially methylated genes were involved in many biological processes, including cell growth, differentiation, adhesion, movement and migration, signal transduction, transcriptional regulation, etc. KEGG-based pathway analysis showed that differentially methylated genes were mainly involved in signaling pathways, such as focal adhesion pathway, cancer pathways, transforming growth factor-β signaling pathway, phosphatidylinositol signaling pathway, melanogenesis pathway, chemokine signaling pathway, adhesion junction pathway, calcium signaling pathway, cell adhesion molecule pathway, mitogen-activated protein kinase signaling pathway, Wnt signaling pathway, Janus kinase-signal transducer and activator of transcription signaling pathway. Based on the criteira "the top 16 most differentially methylated genes related to hypermethylated sites in the promoter region, the genes with the highest methylation frequency (CpG sites ≥ 7) , the genes with certain functions or involved in a certain signaling pathway", 8 genes (KAAG1, DGKE, SOCS2, TFAP2A, GNMT, GALNT3, ANK2 and HOXA9) were selected as candidate biomarkers for melanoma. Conclusion:There are many hypermethylated genes in melanoma tissues, and 8 differentially methylated genes may serve as biomarkers for melanoma.

8.
Article in Chinese | WPRIM | ID: wpr-908662

ABSTRACT

Objective:To study the clinical value of induced sputum DKK3 gene methylation in the evaluation of disease condition and prognosis for non-small cell lung cancer (NSCLC).Methods:Eighty NSCLC patients (observation group) and 50 benign lung disease patients (control group) who were treated in Linshu County People′s Hospital of Shandong Province from January 2015 to December 2017 were enrolled. Methylation specific polymerase chain reaction (PCR) was used to detect the induced sputum DKK3 gene methylation. The DKK3 gene methylation rates in different clinicopathological factors were compared.Results:The DKK3 gene methylation rate in observation group was significantly higher than that in control group: 81.3%(65/80) vs. 2.0%(1/50), the difference was statistically significant ( P<0.05). The DKK3 gene was methylated in lung cancer cells, and was unmethylated in normal lung epithelial cells BEAS-2B. The DKK3 gene methylation rates had correlation with pleural effusion, degree of differentiation, tumor diameter, lymph node metastasis, distant metastasis and TNM staging ( P<0.05). The R0 radicalresection, 3-year survival rate and total survival time in patients with DKK3 gene methylated were significantly lower than those in patient with DKK3 gene unmethylated: 53.8%(35/65) vs. 15/15, 28.1% vs. 37.9%, (1.8 ± 0.3) years vs. (2.1 ± 0.6) years, the differences were statistically significant ( P<0.05). Conclusions:The induced sputum DKK3 gene methylation rate in NSCLC patients is significantly higher and is related with prognosis. The induced sputum DKK3 gene methylation may provide basis for evaluating of disease condition and prognosis for NSCLC patients.

9.
Article in Chinese | WPRIM | ID: wpr-907601

ABSTRACT

N 6-methyladenosine (m 6A) methylation modification is defined as the methylation at the N 6 position of adenosine. This dynamic process is regulated by writer, eraser and reader. Accumulating evidence indicates that m 6A methylation modification is involved in the initiation and development of various digestive system neoplasms including proliferation, invasion, metastasis and chemoresistance. A further understanding about the role of m 6A methylation modification in digestive system neoplasms will benefit the development of a novel precise diagnostic and therapeutic strategy and finally improve the overall prognosis of patients.

10.
Article in Chinese | WPRIM | ID: wpr-907592

ABSTRACT

Lung cancer has the highest mortality rate among malignant tumors, and drug resistance in lung cancer treatment is currently a major challenge for clinical practitioners. Recent studies have found that epigenetics is closely linked to drug resistance in lung cancer, especially in DNA methylation, histone modifications and non-coding RNA regulation. By exploring the mechanisms affecting drug resistance in lung cancer through the above three features and exploring drugs that can effectively improve drug resistance in lung cancer in response to the mechanisms, it can provide ideas for solving the problems related to drug resistance in lung cancer in clinical work and provide a reference basis for prognostic assessment of lung cancer patients.

11.
Article in Chinese | WPRIM | ID: wpr-907532

ABSTRACT

The biological role of N 6-methyladenine (m 6A) methylation modification has been gradually identified, and it has shown increasing value in tumor. In recent years, with the accumulated explore of epigenetics in RNA modification, many studies have reported that m 6A methylation modification contributes to development and progression of lung cancer. m 6A-related modified regulator has potential application value as a clinical target for diagnosis and treatment of lung cancer.

12.
Article in Chinese | WPRIM | ID: wpr-907423

ABSTRACT

Colorectal cancer is a malignant tumor occurring in the colon or rectum, which has a high incidence rate. In order to improve the prognosis of colorectal cancer, the pathogenesis of colorectal cancer still needs to be further clarified. Epigenetics can directly affect the progression and metastasis of colorectal cancer, and histone methylation is an important means of histone modification, which can regulate the transcriptional activation and inhibition of downstream genes. A large number of studies have confirmed the effects of histone methylation on the progression of colorectal cancer, and inhibitors of related methylation and demethylation may play a role as potential therapeutic drugs for colorectal cancer. In this article, the colorectal cancer and its related methylation regulation were introduced, the types of histone methylation modifications and their regulation were summarized, and the regulation of histone methyltransferases and demethylases involved in the progression of colorectal cancer was demonstrated. In addition, the potential significance of histone methylation inhibitors for the treatment of colorectal cancer was summarized, and the possibility of related inhibitors as treatment drugs for colorectal cancer was explored.

13.
Article in Chinese | WPRIM | ID: wpr-907245

ABSTRACT

Bronchopulmonary dysplasia(BPD)is a chronic pulmonary disease related to preterm neonatal.The pathogenesis of BPD hasn′t been clear now.But we have already known extracellular matrix remodeling has played an important role in alveoli dysplasia.We have found epigenetics has participated in extracellular matrix remodeling.There is a strict balance between the composition and decomposition of the ECM under the physiology state.However the ECM will reconstruct when its component change, which would influence the normal physiology process and lead to the disease.The review describes DNA methylation′s and microRNAs′ functions in extracellular matrix remodeling of BPD.This may help us understand the pathogenesis of BPD, and may offer some new methods to prevent or cure BPD.

14.
Article in Chinese | WPRIM | ID: wpr-905865

ABSTRACT

Objective:To investigate the mechanism of Shugan Bushen Yulin decoction in inhibiting voltage-dependent anion-selective channel protein 2 (VDAC2) gene methylation, affecting sperm mitochondrial function, and improving sperm motility through the cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) pathway. Method:Forty male SD rats were randomly divided into the blank group, model group, high- and low-dose Shugan Bushen Yulin decoction groups, and L-carnitine group, with eight rats in each group. Adenine (0.05 g·kg<sup>-1</sup>) was administered by gavage for 14 d for inducing oligospermia and asthenospermia. Rats in the Shugan Bushen Yulin decoction groups were treated with intragastric administration of 32.4, 8.1 g·kg<sup>-1 </sup>Shugan Bushen Yulin decoction, respectively, while those in the L-carnitine group received 0.27 g·kg<sup>-1</sup> L-carnitine by gavage. Following the measurement of sperm motility using an automatic sperm analyzer, the pathological changes in testicular tissue were observed by hematoxylin-eosin (HE) staining. Sperm mitochondrial membrane potential was detected by flow cytometry. The expression of VDAC2 in the testicular tissue was determined by immunofluorescence assay. Real-time polymerase chain reaction (Real-time PCR) was conducted for detecting VDAC2 mRNA expression in testicular tissue. The methylation of VDAC2 gene was examined using bisulfite sequencing. The cAMP expression in testicular tissue was detected by enzyme-linked immunosorbent assay (ELISA), and the PKA protein expression in testicular tissue by Western blot. Result:Compared with the blank group, the model group exhibited significantly decreased sperm density and motility (<italic>P</italic><0.01), increased mitochondrial membrane potential (<italic>P</italic><0.01), down-regulated VDAC2 mRNA and protein expression, PKA protein expression, and cAMP content in testicular tissue (<italic>P</italic><0.01), and elevated VDAC2 gene methylation (<italic>P</italic><0.01). Compared with the model group, L-carnitine and Shugan Bushen Yulin decoction at the high and low doses all remarkably increased the sperm density and motility and mitochondrial membrane potential (<italic>P</italic><0.01), up-regulated VDAC2 mRNA and protein expression, PKA protein expression, and cAMP content in the testicular tissue (<italic>P</italic><0.01), and lowered the methylation of VDAC2 in testicular tissue (<italic>P</italic><0.01). The comparison with the L-carnitine group showed that the sperm density and motility and mitochondrial membrane potential in the low-dose Shugan Bushen Yulin decoction group declined significantly (<italic>P</italic><0.01). The VDAC2 mRNA and protein expression, PKA protein expression, and cAMP content in the testicular tissue were significantly down-regulated (<italic>P</italic><0.01), while the methylation of VDAC2 was significantly enhanced (<italic>P</italic><0.01). Conclusion:Shugan Bushen Yulint decoction may inhibit VDAC2 gene methylation, increase VDAC2 expression, regulate cAMP/PKA pathway, and change mitochondrial membrane potential to enhance the sperm motility.

15.
Journal of Clinical Hepatology ; (12): 2719-2722, 2021.
Article in Chinese | WPRIM | ID: wpr-905029

ABSTRACT

N 6 -methyladenosine (m6A) is a chemical modification that exists in a variety of RNAs and is most commonly observed in mRNA. The liver is a vital metabolic and digestive organ in human body, and m6A methylation plays an important role in the physiological and pathological processes of the liver. This article reviews the biological role and potential application value of m6A methylation in liver physiology and liver diseases such as viral hepatitis, nonalcoholic fatty liver disease, liver fibrosis, and hepatocellular carcinoma, and it is pointed out that m6A methylation can regulate related factors and is involved in the development and progression of liver diseases, which provides new ideas and targets for clinical diagnosis and treatment.

17.
Chinese Journal of Lung Cancer ; (12): 490-496, 2021.
Article in Chinese | WPRIM | ID: wpr-888591

ABSTRACT

BACKGROUND@#Lung cancer is the most common malignant tumor in clinic. The prognosis of advanced patients is poor, and the 5-year survival rate is low. Therefore, early diagnosis becomes the key to improve the prognosis of patients. In recent years, with the development of molecular biology technology, aberrant modification of some driver genes, such as methylation, has become an important method for early diagnosis of lung cancer. The purpose of the present work was to quantitatively evaluate the diagnostic value of abnormal hypermethylation in short state homeobox 2 (SHOX2) promoter region in lung cancer by evidence-based medicine.@*METHODS@#We searched MEDLINE, EMBASE, Ovid, Web of Science and CNKI for literatures related to the relationship between SHOX2 gene promoter hypermethylation and lung cancer. The data of SHOX2 promoter hymethylation in the original study were extracted. The diagnostic sensitivity, specificity and area under receiver operating characteristic (ROC) curve of SHOX2 promoter methylation were calculated.@*RESULTS@#Finally, 13 publications were included in this meta-analysis, and due to significant statistical heterogeneity among the studies (P<0.05) the data was pooled by random effect model. The diagnostic sensitivity and specificity of SHOX2 promoter hypermethylation in the diagnosis of lung cancer were 0.75 (95%CI: 0.74-0.77) and 0.89 (95%CI: 0.88-0.91), respectively; The positive likelihood ratio value was 6.75 (4.56-9.99), and the negative predictive value was 0.36 (0.25-0.52); The diagnostic odds ratio was 23.16 (11.34-47.31), and the area under the ROC curve was 0.9.@*CONCLUSIONS@#SHOX2 gene promoter hypermethylation is high in serum, broncholavage fluid and pleural effusion of lung cancer patients, which can be used as a biomarker for auxiliary diagnosis of lung cancer.

18.
Asian Journal of Andrology ; (6): 472-478, 2021.
Article in English | WPRIM | ID: wpr-888455

ABSTRACT

Epigenetic changes are potentially important for the ontogeny and progression of tumors but are not usually studied because of the complexity of analyzing transcript regulation resulting from epigenetic alterations. Prostate cancer (PCa) is characterized by variable clinical manifestations and frequently unpredictable outcomes. We performed an expression quantitative trait loci (eQTL) analysis to identify the genomic regions that regulate gene expression in PCa and identified a relationship between DNA methylation and clinical information. Using multi-level information published in The Cancer Genome Atlas, we performed eQTL-based analyses on DNA methylation and gene expression. To better interpret these data, we correlated loci and clinical indexes to identify the important loci for both PCa development and progression. Our data demonstrated that although only a small proportion of genes are regulated via DNA methylation in PCa, these genes are enriched in important cancer-related groups. In addition, single nucleotide polymorphism analysis identified the locations of CpG sites and genes within at-risk loci, including the 19q13.2-q13.43 and 16q22.2-q23.1 loci. Further, an epigenetic association study of clinical indexes detected risk loci and pyrosequencing for site validation. Although DNA methylation-regulated genes across PCa samples are a small proportion, the associated genes play important roles in PCa carcinogenesis.

19.
Article in Chinese | WPRIM | ID: wpr-878987

ABSTRACT

To investigate the effect of Gegen Qinlian Decoction(GQD) on enzyme activity, gene expression and methylation level of fatty acid synthase(FASN) in adipose tissue from rats with insulin resistance induced by high-fat diet. The 60% fat-powered high-fat diet was continuously given to male SD rats to induce the insulin resistance model. Then, they were divided into five groups randomly and administrated by gavage every day for 16 weeks with following drugs respectively: 10 mL·kg~(-1)water for control group(C) and insulin resistance model control group(IR), 1.65 g·kg~(-1)GQD per day for low-dose group(GQDL), 4.95 g·kg~(-1)GQD per day for medium-dose group(GQDM), 14.85 g·kg~(-1)GQD per day for high-dose group(GQDH), and 5 mg·kg~(-1) rosiglitazone per day for rosiglitazone group(RGN). Epididymal adipose tissue was taken to determine enzyme activity of FASN by colorimetric method, mRNA expression level of Fasn by quantitative Real-time PCR(Q-PCR) and CpGs methylation level between +313 and +582 by bisulfite sequencing PCR(BSP). These results showed that Fasn expression was significantly lowered in IR model rats compared with the control rats(P<0.01). Enzymatic activity and CpGs methylation level of Fasn in IR group showed downward trends. Low and medium-dose GQD can increase enzyme activity of FASN(P<0.05). Moreover, low-dose GQD increased the total CpGs methylation level of Fasn fragment between +313 and +582 in insulin resistance rats(P<0.05). For GQDM group, the methylation frequency of CpGs at positions +506 and +508(P<0.01) as well as the methylation frequency of CpGs on the binding sites of transcription factorzinc finger protein 161(P<0.05) were significantly increased. The methylation frequency of CpG at +442 position was positively correlated with Fasn expression(P<0.01, r=0.735), and methylation frequencies of CpGs at +345 and +366 positions were positively associated to enzyme activity of FASN respectively(P<0.05, r=0.479; P<0.01, r=0.640). In conclusion, GQD can reverse enzyme activity of FASN and methylation level of Fasn in adipose tissue of insulin resistant rats, and CpG sites at positions +506 and +508 may be the targets of GQD. The methylation level of CpGs at + 345 and + 366 sites were possibly related to FASN activity, while methylation of CpG at + 442 site may be closely correlated with mRNA level of Fasn. In addition, GQD did not significantly change mRNA expression level of Fasn, but effectively reversed enzymatic activity, suggesting that GQD may regulate the post transcriptional expression of Fasn.


Subject(s)
Adipose Tissue , Animals , Drugs, Chinese Herbal , Fatty Acid Synthases/genetics , Gene Expression , Insulin Resistance/genetics , Male , Methylation , Rats , Rats, Sprague-Dawley
20.
Article in Chinese | WPRIM | ID: wpr-881401

ABSTRACT

@#Protein arginine methyltransferases, which proceed the post-translational modification of both histones and non-histones, play an important role in many biological pathways. Protein arginine methyltransferase 5 (PRMT5) is a major enzyme responsible for symmetric di-methylation of arginine residues and has been suggested as a potential therapeutic target for tumors.In the past decade,the discovery and development of PRMT5 inhibitors have become one of the most important research fields.This article introduces the structure and biochemical function of PRMT5 and its correlation with cancer reviews, the binding modes and biological data of PRMT5 inhibitors under development, and discusses the clinical application potential of PRMT5 inhibitors in the treatment of cancer.

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