中国肿瘤生物治疗杂志2017,Vol.24Issue(9):972-978,7.DOI:10.3872/j.issn.1007-385x.2017.09.008
miR-6803和PPP6R1在食管鳞状细胞癌组织和细胞中的表达及其甲基化状态与患者临床病理特征的关系
Expression and methylation status of miRNA-6803 and PPP6R1 in esophageal squamous cell carcinoma and their relationship with clinicopathological characteristics of ESCC patients
摘要
Abstract
Objective:To investigate the expression of microRNA-6803(miR-6803) and its host gene PPP6R1 in esophageal squamous cell carcinoma (ESCC) and the role of promoter methylation status of PPP6R1 in the tumorigenisis and progression of ESCC.Methods:ESCC tissues and corresponding para-cancerous tissues from 72 cases of ESCC patients stored in the bio-specimen base of the Fourth Hospital Affiliated to Heibei Medical University during 2013 and 2014 were collected for this study.Real-time fluorescence quantitative PCR (qPCR) was used to detect the expression of miR-6803/PPP6R1 in collected tissues and in ESCC cell lines (TE1,TE13,Eca109,T.TN,Kyse170) treated or untreated with DNA methyl-transferase inhibitor 5-aza-2'-detoxycytidine (5-Aza-dC).Methylation specific PCR (MSP) method was used to detect the methylation status of PPP6R1 in esophageal cancer cell lines and collected tissues,respectively.Results:The relative expressions of miR-6803 and PPP6R1 in ESCC tissues were significantly reduced compared to correspondingtissues (0.318±0.156,0.408±0.177 vs 1.000±0.001,all P< 0.05),and expression of miR-6803 was associated with lymph node metastasis,TNM stage and pathological differentiation (all P<0.05);The expression of PPP6R1 was associated with TNM stage and pathological differentiation (all P<0.05).There was a significant correlation between the relative expression of miR-6803 and PPP6R1 in ESCC tissues (P<0.05).The promoter methylation frequency of PPP6R1 in ESCC tissues was significantly higher than that in corresponding normal tissues (56.94% vs 36.11%,P<0.05),and was also associated with TNM stage and pathological differentiation (all P<0.05).The low expression of miR-6803/PPP6R1 was significantly correlated with promoter methylation of PPP6R1 in ESCC tissues (P<0.05).The relative expression level of miR-6803 and PPP6R1 in 5 ESCC cell lines was enhanced after the treatment with 5-Aza-dC.After treatment with 5-Aza-dC,the methylation level of PPP6R1 was decreased in TEl,TEl3,Kysel70 cells,while complete unmethylation of PPP6R1 was detected in other two cell lines.Conclusion:Aberrant low expression of miR-6803 and its host gene PPP6R1 are closely related to the occurrence and development of ESCC,and promoter methylation may be one of the mechanisms for inactivation of miR-6803/PPP6R1 in ESCC.关键词
食管鳞状细胞癌/微小RNA-6803/蛋白磷酸酶6调节亚单位1(PPP6R1)基因/甲基化Key words
esophageal squamous cell carcinoma/microRNA-6803(miR-6803)/protein phosphatase 6 regulates subunit 1 (PPP6R1)gene/methylation分类
医药卫生引用本文复制引用
沈素朋,徐凤楼,刘江惠,卢帆,梁佳,郭炜,董稚明..miR-6803和PPP6R1在食管鳞状细胞癌组织和细胞中的表达及其甲基化状态与患者临床病理特征的关系[J].中国肿瘤生物治疗杂志,2017,24(9):972-978,7.基金项目
国家自然科学基金资助项目(No.81572441) (No.81572441)
河北省医学科学研究重点课题(No.20170700,No.20170701). Projects supported by the National Natural Science Foundation of China (No.81572441),and the Key Project of Medical Science Research of Hebei Province (No.20170700,No.20170701) (No.20170700,No.20170701)