MiRNA-34b/c And MiRNA-124a DNA Methylation Study In Gastric Cancer

Objective:miRNA is a kind of noncoding RNAs in eukaryote with the length of 22 to 28 nucleotides, which take part in the growth regulation of organism. Abnormal expression of miRNAs may contribute to tumourgenesis, affecting its development and prognoses. miRNA-34b/c and miRNA-124a are widely expressed in human organs, but the expressions of miRNA-34b/c and miRNA-124a are relatively low in some malignant tumors, the expression of miRNA-34b/c and miRNA-124a in gastric cancer are lower than in normal gastric mucosa. Methylation of miRNA DNA could reduce it's expression. In our study we detected the methylation status of miRNA-34b/c and miRNA-124a DNA promoter to discusse the influence of methylation on the expression of miRNAs. Cyclin-dependent kinase 6(CDK6) is quite related with gastric cancer, and it is the target molecule of miRNA-34b/c and miRNA-124a;we also detected the expression of CDK6 in gastric cancer tissue and normal gastric mucosa, analyzed the relationship between miRNAs DNA methylation and CDK6 in gastric cancer, in order to reveal the pathogenesis of gastric cancer and to search new molecular markers for cancer detection.Methods:1 According to different pathological results, the 80 endoscopic biopsy specimens were divided into two groups:normal control group and gastric carcinoma group. Gastric carcinoma group, according to different histological types, was divided into adenocarcinoma, signet-ring cell carcinoma and undifferentiated carcinoma group, according to different differentiation degree, was divided into well-differentiated, moderately-differentiated and poorly-differentiated group; according to different lymphatic metastasis, was divided into lymphatic metastasis positive and negative group; according to clinical stages, was divided intoâ… +â…¡andâ…¢+â…£group.2 DNA was extracted and dealt with Sulfite. Detect the methylation status of miRNA-34b/c and miRNA-124a DNA promoter.3 Immunohistochemical SP methods were applied to detect the expression of CDK6. Analyze the expression of CDK6 in the tissues. Results:1 The methylation rate of miRNA-34b/c and miRNA-124a DNA promoter in normal control group and gastric carcinoma group were statistically different (P<0.05).2 The methylation rate of miRNA-124a DNA promoter in well-differentiated, moderately-differentiated and poorly-differentiated group were statistically different (P<0.05).The methylation rate of miRNA-34b/c DNA promoter in the lymphatic metastasis positive group and negative group were statistically different (P<0.05).3 The rate of specimens with miRNA-34b/c and miRNA-124a DNA promoter hypermethylation positive was 30%,with one of them positive was 40% and with none of them positive was 30%. There was statistically difference of the probability distribution inâ… +â…¡andâ…¢+â…£group (P<0.05).4 The positive rate of CDK6 expression in gastric cancer tissue and normal controls were statistically different (P<0.05).5 There was a significantly positive relationship berween the methylation of miRNA-34b/c,miRNA-124a DNA promoter and the expression intensity of CDK6(r=0.658, P<0.05)Conclusion:1 The methylation of miRNA-34b/c,miRNA-124a DNA promoter may occur in gastric cancer.2 Methylation of miRNA-34b/c DNA promoter was significantly correlated with lymphatic metastasis; Methylation of miRNA-124a DNA promoter was significantly correlated with the pathological differentiation degrees.3 The number of miRNA DNAs that with hypermethylation status was significantly correlated with clinical stages reveals that the occurrence and development of gastric cancer could affected by many miRNA DNAs with promoter methylation positive.4 The relationship between the methylation of miRNA-34b/c,miRNA-124a DNA promoter and the expression intensity of CDK6, reveals the significant role of miRNA and methylation modification in the development of gastric cancer.