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The Expression Of MiRNA-124a Associated With Pathologic Features In Gastric Carcinoma

Posted on:2012-09-26Degree:MasterType:Thesis
Country:ChinaCandidate:F ChenFull Text:PDF
GTID:2214330335998953Subject:Internal Medicine
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Object ive:MicroRNA-124a is widely expressed in many tissues, but the relationship between miRNA-124a and gastric carcinoma is poorly understood. Some miRNA genes harboring CpG islands undergo methylation-mediated silencing. Our study aimed to detect the expression of miRNA-124a in gastric carcinoma by qRT-PCR, explore the relationship between its expression and the methylation of miRNA-124a gene promoter to reveal pathogenesis of gastric carcinoma.Methods:1. Eighty specimens including forty gastric carcinoma and forty normal gastric tissues were flash frozen by the endoscopy biopsy. Clinical and pathological data were retrieved from clinical databases as well as from the original pathology reports, including histological grade,differentiation,nodal metastases and tumour stage.2. RNA was extracted by Trizol. qRT-PCR was used to quantify the expression level of miRNA-124a.3. MiRNA-124a gene promoter methylation status was established by PCR analysis of bisulfite-modified genomic DNA.Results:1. The expression of miRNA-124a in gastric carcinoma group was significantly lower than normal control group (P<0.05).2. The relationship between miRNA-124a and the clinicopathologic features.2.1 The miRNA-124a was differentially expressed in three different histological subtypes of gastric carcinomas (adenocarcinoma, signet-ring cell carcinoma and undifferentiated carcinoma), however, this was no statistically significant(P>0.05).2.2 The expression of miRNA-124a was significantly higher in well-differentiated group than poorly-differentiated group (P<0.05).2.3 No significant difference was observed between the lymphatic metastasis positive group and negative group (P>0.05).2.4 No significant difference was observed betweenâ… +â…¡andâ…¢+â…£group (P>0.05).3. Higher methylation rate of miRNA-124a gene promoter expression was present in gastric carcinoma group than normal control group (P<0.05).4. The relationship between the methylation of miRNA-124a gene promoter and the clinicopathologic features.4.1 The methylation rate of miRNA-124a gene promoter was differentially expressed in three different histological subtypes of gastric carcinomas (adenocarcinoma, signet-ring cell carcinoma and undifferentiated carcinoma), however, this was no statistically significant (P>0.05).4.2 The methylation rate of miRNA-124a gene promoter was significantly higher in poorly-differentiated group than well-differentiated group (P<0.05).4.3 No significant difference was observed between lymphatic metastasis positive group and negative group (P>0.05).4.4 No significant difference was observed betweenâ… +â…¡andâ…¢+â…£groups (P>0.05).Conclusion:1. The expression of miRNA-124a was downregulated in gastric carcinoma, miRNA-124a was inversely correlated with methylation status. This indicated that miRNA-124a was a novel tumor-suppressive miRNA, miRNA-124a undergone aberrant DNA methylation-associated silencing in gastric carcinoma.2. The expression of miRNA-124a were significantly correlated with the pathological differentiation degree so that miRNA-124a could be used as a molecular marker for cancer detection.3. The methylation of miRNA-124a gene promoter were significantly correlated with the pathological differentiation degree. Methylation alterations may have widespread biological and clinical significance.
Keywords/Search Tags:miRNA-124a, gastric carcinoma, MSP, qRT-PCR, gene methylation
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