Li Albert S M, Siu Michelle K Y, Zhang HuiJuan, Wong Esther S Y, Chan Kelvin Y K, Ngan Hextan Y S, Cheung Annie N Y
Department of Pathology, Queen Mary Hospital, Hong Kong, China.
Reprod Sci. 2008 Sep;15(7):735-44. doi: 10.1177/1933719108322433.
This study investigated the expression and methylation profiles of SOX2, a stem cell-related transcription factor, in placentas and gestational trophoblastic disease. The methylation status of SOX2 promoter region in 55 hydatidiform moles, 4 choriocarcinoma, 23 first trimester, and 15 term placentas was evaluated by methylation-specific polymerase chain reaction. The methylated allele was found in 4.4% (1/23) of first trimester placentas, 26.7% (4/15) term placentas, and 56.4% (31/55) of hydatidiform moles and all choriocarcinoma samples and cell lines. A significant reduction in SOX2 messenger RNA expression was found in the hydatidiform moles (P = .027) when compared with that in the placentas. SOX2 messenger RNA expression was significantly correlated with SOX2 hypermethylation (P < .001). SOX2 expression was restored in choriocarcinoma cell lines following treatment to 5-Aza-2(')-deoxycytidine and/or Trichostatin A, demethylation and histone deacetylase inhibitors, respectively, and the response was synergistic. Epigenetic mechanisms may play important role on the transcriptional regulation of SOX2 and contribute to pathogenesis of gestational trophoblastic disease.
本研究调查了干细胞相关转录因子SOX2在胎盘和妊娠滋养细胞疾病中的表达及甲基化谱。采用甲基化特异性聚合酶链反应评估了55例葡萄胎、4例绒毛膜癌、23例孕早期胎盘和15例足月胎盘组织中SOX2启动子区域的甲基化状态。在23例孕早期胎盘组织中有4.4%（1/23）、15例足月胎盘组织中有26.7%（4/15）、55例葡萄胎中有56.4%（31/55）检测到甲基化等位基因，且所有绒毛膜癌样本及细胞系均检测到甲基化等位基因。与胎盘组织相比，葡萄胎组织中SOX2信使核糖核酸表达显著降低（P = 0.027）。SOX2信使核糖核酸表达与SOX2高甲基化显著相关（P < 0.001）。分别用5-氮杂-2'-脱氧胞苷和曲古抑菌素A（脱甲基和组蛋白去乙酰化酶抑制剂）处理绒毛膜癌细胞系后，SOX2表达得以恢复，且呈协同反应。表观遗传机制可能在SOX2的转录调控中起重要作用，并参与妊娠滋养细胞疾病的发病机制。
