摘要
目的检测大肠癌(CRC)中IL-6、SOCS3基因mRNA表达和启动子甲基化状态,以及STAT3基因mRNA表达水平,探讨大肠癌中IL-6、SOCS3基因表观遗传学改变及其对IL-6/STAT3通路的影响。方法实时荧光定量PCR检测20例CRC癌组织及癌旁组织IL-6、SOCS3及STAT3基因mRNA水平,甲基化特异性PCR(MSP)检测SOCS3甲基化状态,亚硫酸氢盐测序(BSP)检测IL-6启动子甲基化状态。结果与癌旁组织相比,癌组织中IL-6、STAT3 mRNA表达显著增高(P<0.05),而SOCS3显著降低,IL-6与SOCS3表达呈负相关;癌组织中IL-6启动子-633、-611、-575、-575bp位点甲基化水平均降低,而SOCS3则呈现高度甲基化状态(P<0.05)。结论大肠癌中IL-6和SOCS3基因DNA甲基化状态异常,影响基因表达,从而诱导IL-6/STAT3信号转导通路持续活化,促进了大肠癌的发生发展。
Abstract： Objective To detect the methylation status,mRNA expression of IL-6 and SOCS3 genes and the mRNA ex- pression of STAT3 gene as well in colorectal cancer （CRC）. Furtherly,to explore the effect of methylation of IL-6 on SOCS3 gene expression and consequently on the IL-6/STAT3 pathway. Methods The expressions of IL-6, SOCS3, STAT3 mRNA were detected by quantitative reverse transcription polymerase chain reaction （QRT-PCR）. The methylation status of SOCS3 and IL- 6 genes promoter CpG island were assayed by methylation specific PCR （MSP） and bisulfite sequencing PCR （BSP） ,respec- tively. Results The expressions of IL-6, STAT3 in CRC were significantly up-regulated, while SOCS3 expression was signifi- cantly reduced. There was a negative correlation between IL-6 and SOCS3 expression in cancer tissue; Moreover, SOCS3 was shown and the methylation levels of IL-6 start sub -633 ,-611 ,-575 ,-575bp sites were much lower in cancer tissue than those in the adjacent tissues （ P 〈 0. 05 ）. Conclusion Abnormal methylation status of IL-6 and SOCS3 caused gene expression chan- ges and induced activation of the IL-6/STAT3 signaling pathway ,which may contribute to the pathogenesis of colorectal cancer.
出处
《临床消化病杂志》
2013年第6期337-341,共5页
Chinese Journal of Clinical Gastroenterology
基金
湖北省自然科学基金(2011CDB530)
国家自然科学基金面上项目(81270468)
