Expression Difference and Its Mechanisms of miR-497 and miR-34a in Platinum-sensitive and Platinum-re-sistant Epithelial Ovarian Carcinoma Patients
10.6039/j.issn.1001-0408.2017.17.02
- VernacularTitle:miR-497和miR-34a在铂敏感和铂耐药卵巢上皮癌患者中的表达差异及机制研究
- Author:
Lijuan CAO
;
Wenbo LIU
- Keywords:
MicroRNAs;
miR-497;
miR-34a;
Epithelial ovarian cancer;
Platinum resistant;
DNA methylation;
Histone meth-ylation;
Promoter region
- From:
China Pharmacy
2017;28(17):2308-2313
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the expression difference and its mechanism of miR-497 and miR-34a in platinum-sen-sitive and platinum-resistant epithelial ovarian carcinoma(EOC)patients. METHODS:A total of 72 EOC patients underwent ovari-an cancer staging surgery or cytoreductive surgery were selected from department of gynaecology and obstetriscs of our hospital dur-ing Jan. 2008-Jan. 2012. They received standardized platinum chemotherapy after surgery and were followed up (during Jul.2008-Jul.2016). According to the sensitivity to platinum,those patients were divided into platinum-sensitive group (42 cases) and platinum-resistant group (30 cases) . Real-time fluorescent quantitative PCR was adopted to detect the expression of miR-497 and miR-34a in tumor tissue,and the relationship of it with total survival period was investigated. The levels of DNA methylation of miR-497 and miR-34a promoter region were determined by nest type land type methylation specific PCR. Western blot assay was used to detect the H3K9 dimethylation(H3K9me2)levels. The H3K9me2 levels of miR-497 and miR-34a promoter region were de-termined by chromatin immunoprecipitation method. RESULTS:The expression levels of miR-497 and miR-34a in platinum-sensi-tive group were significantly higher than platinum-resistant group,with statistical significance (P<0.05). Total survival period of 72 patients was(45.7±17.5)months,which was positively correlated with the expression levels of miR-497 and miR-34a(r2 were 0.2714,0.3782,P<0.01). The DNA methylation of miR-497 and miR-34a promoter region in platinum-resistant group was signif-icantly higher than platinum-sensitive group,and H3K9me2 level of promoter region was significantly higher than platinum-sensi-tive group,with statistical significance (P<0.05 or P<0.01). H3K9me2 levels of platinum-resistant group were slightly higher than that of platinum-sensitive group,but there was no statistical significance (P>0.05). CONCLUSIONS:The expression of miR-497 and miR-34a in tumor tissue of EOC patients are related to the sensitivity of platinum chemotherapy and the survival time of patients. DNA methylation and histone methylation of promoter region may be one of the mechanisms of their expression changes.
