Occurrence of HHIP gene CpG island methylation in gastric cancer.
Occurrence of HHIP gene CpG island methylation in gastric cancer.
复制标题
DOI：
10.3892/ol.2014.2518
复制
发表时间：
2014-11
期刊：
影响因子：
2.9
通讯作者：
Zuo Y
中科院分区：
文献类型：
--
作者：
Song Y;Zuo Y
本研究旨在观察胃癌组织、癌旁组织及AGS细胞系中HHIP基因CpG岛甲基化状态，分析HHIP基因CpG岛甲基化与胃癌发生的关系。应用逆转录聚合酶链反应（RT-PCR）检测了60例胃癌组织、癌旁组织及胃癌AGS细胞系中HHIP mRNA的表达。采用甲基化特异性PCR（MSP）检测胃癌组织及癌旁组织中HHIP基因启动子区甲基化状态。用甲基转移酶抑制剂5-aza-dc处理AGS细胞前后，分别用RT-PCR、MSP和BSP检测HHIP mRNA表达水平、启动子区甲基化状态和CpG岛甲基化位点。分析HHIP启动子区CpG岛甲基化状态与HHIP mRNA表达水平的相关性。胃癌组织中HHIP mRNA的表达水平显著低于癌旁组织（0.82±0.38 vs.1.60 ±0.26; P<0.001）。HHIP mRNA的表达与年龄、性别、肿瘤分期、分化程度、淋巴结转移无明显相关性（P>0.05）。癌旁组织HHIP基因启动子区甲基化率（17.7±3.59%）明显低于胃癌组织（62.9±6.14%）和AGS细胞（99.7±0.67%）（P<0.05）。与5-aza-dc干预前相比，干预后AGS细胞中HHIP mRNA的表达水平显著升高（0.21±0.12 vs.4.68 ±0.22; P<0.01），而AGS细胞的甲基化程度明显降低（90.2± 0.67vs.10.1 ±0.21%; P<0.01），CpG岛甲基化位点明显减少。HHIP甲基化程度与mRNA表达水平呈负相关（r=-0.693; P<0.01）。推测胃癌组织和细胞中HHIP基因启动子CpG岛高度甲基化导致HHIP mRNA表达降低，可能参与胃癌的发生。
The present study aimed to observe the methylation status of the CpG islands at the human hedgehog interacting protein (HHIP) gene in gastric cancer tissues, peritumoral tissues and the AGS cell line, to analyze the association between the methylation status of the CpG islands and the tumorigenesis of gastric cancer. The HHIP mRNA expression in 60 human gastric carcinnoma tissues, peritumoral tissues and the gastric carcinoma AGS cell line were detected by reverse transcription polymerase chain reaction (RT-PCR). The HHIP methylation status of the promoter region in the gastric carcinnoma tissues and peritumoral tissues was detected by methylation-specific PCR (MSP). Prior to and following treatment with methyl transferase inhibitor 5-aza-2′-deoxycitydine (5-aza-dc), the HHIP mRNA expression level, the methylation status of the promoter region and the methylation site loci on the CpG islands in the AGS cells were detected by RT-PCR, MSP and bisulfite sequencing PCR (BSP), respectively. The correlation between the methylation status of the CpG islands at the HHIP promoter region and the HHIP mRNA expression level were analyzed. It was found that the expression level of the HHIP mRNA in the gastric carcinoma tissues was significantly lower than that in the adjacent tissues (0.82±0.38 vs. 1.60±0.26, respectively; P<0.001). No significant correlations were observed between the expression of HHIP mRNA and age, gender, tumor-node-metastasis stage, differentiation degree and presence of lymph node metastasis (P>0.05). The degree of methylation of the HHIP gene promotor in the peritumoral tissues (17.7±3.59%) was significantly lower than that in the gastric cancer tissues (62.9±6.14%) and in the AGS cells (99.7±0.67%) (P<0.05). Compared with prior to 5-aza-dc intervention, the HHIP mRNA expression level in the AGS cells was significantly increased subsequent to intervention (0.21±0.12 vs. 4.68±0.22; P<0.01), while the degree of methylation in the AGS cells was significantly decreased (90.2±0.67 vs. 10.1±0.21%; P<0.01), and the methylation sites in CpG islands were significantly reduced. The degree of HHIP methylation showed a negative correlation with the level of mRNA expression (r=−0.693; P<0.01). It can be hypothesized that a high degree of methylation of the HHIP gene promoter CpG islands in gastric cancer tissues and cells causes a decrease in HHIP mRNA expression, which may be involved in the carcinogenesis of gastric cancer.
登录
查看更多内容
影响因子：
9.3
作者：
Eising E;A Datson N;van den Maagdenberg AM;Ferrari MD
通讯作者：
Ferrari MD
影响因子：
9.7
作者：
Valadez, J. Gerardo;Grover, Vandana K.;Carter, Melissa D.;Calcutt, M. Wade;Abiria, Sunday A.;Lundberg, Christopher J.;Williams, Thomas V.;Cooper, Michael K.
通讯作者：
Cooper, Michael K.
影响因子：
7.9
作者：
Hodes GE
通讯作者：
Hodes GE
影响因子：
4.3
作者：
Bollschweiler, Elfriede;Berlth, Felix;Hoelscher, Arnulf H.
通讯作者：
Hoelscher, Arnulf H.
DOI：
10.1159/000337543
发表时间：
2012-01-01
期刊：
CLEFT LIP AND PALATE: EPIDEMIOLOGY, AETIOLOGY AND TREATMENT
影响因子：
--
作者：
Cobourne, Martyn T.;Green, Jeremy B. A.
通讯作者：
Green, Jeremy B. A.