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Archive > Volume 20 Issue 5 > 2013,20(5):590-596. DOI:10.3872/j.issn.1007-385X.2013.05.015 Prev Next
Clinical Research
High methylation level of CpG island in HHIP gene participates in the occurrence of gastric cancer
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Abstract:
Objective : To Observe the methylation level of CpG island in human hedgehog interacting protein (HHIP) gene in gastric cancer tissues, peritumoral tissues and AGS cells, and to explore the relationship between the methylation level of CpG island and the tumorigenesis of gastric cancer. Methods: The expressions of HHIP mRNA in 30 human gastric carcinnoma tissues, peritumoral tissues and gastric carcinoma AGS cells were detected by RT-PCR. The expressions of HHIP and the methylation level of promoter region of HHIP gene in gastric carcinnoma tissues and peritumoral tissues were detected by immunohistochemical staining and methylation specific PCR (MSP), respectively. Before and after the treatment of methyl transferase inhibitor 5-Aza-2′-deoxycitydine (5-Aza-dc), the HHIP mRNA expression, methylation level of promoter region and methylation sites locus on CpG island in AGS cells were detected by RT-PCR, MSP and bisulfite sequencing PCR(BSP), respectively. The correlation between the methylation status of CpG island at HHIP promoter region and HHIP mRNA expression level was analyzed. Results: The expression of HHIP mRNA (0.82±0.38 vs 1.60±0.26, P=0.000) and HHIP (0.5±0.03 vs 0.8±0.27, P<0.05) in gastric carcinoma was significantly lower than that in the peritumoral tissues. No significant correlation was observed between the expression of HHIP mRNA or protein and age, sex, TNM stage, differentiation degree and lymph node metastasis (P>0.05). The methylation level of HHIP gene promtor in the peritumoral tissues was significantly higher than that in the gastric cancer tissues and AGS cells (\[17.7±359\]% vs \[62.9±6.14\]%, \[99.7±0.67\]%; all P<0.05). Compared with that before 5-Aza-dc treatment, the HHIP mRNA expression in AGS cells was significantly increased after treatment (4.68±0.22 vs 0.21±0.12, P<001), while the methylation level of AGS cells decreased significantly (\[10.1±0.21\]% vs \[90.2±0.67\]%, P<001), and the methylation sites in CpG islands were significantly reduced. The degree of HHIP methylation showed a negative correlation with the mRNA expression(r=-0.693, P=0.00). Conclusion: High methylation level of CpG island in HHIP gene promoter may increase the expression of HHIP gene, and then be involved in the carcinogenesis of gastric cancer.
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Project Supported:
Project supported by the Social Development Plan of Zhangjiagang in 2012（No. ZKS1211）
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