Transcription Factor WT1 and Promoter CpG Hypomethylation Coactivate HOXA10 Expression in Ovarian Cancer

Transcription Factor WT1 and Promoter CpG Hypomethylation Coactivate HOXA10 Expression in Ovarian Cancer
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转录因子 WT1 和启动子 CpG 低甲基化共同激活卵巢癌中 HOXA10 的表达

DOI:
10.2174/13816128113199990545
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发表时间:
2014-04-01
影响因子:
3.1
通讯作者:
Cheng, Wenjun
Cheng, Wenjun
中科院分区:
医学4区
文献类型:
--
作者:
Jiang, Yi;Chu, Yongli;Cheng, Wenjun

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HOXA 10在机体结构和发育中起着重要作用。最近,HOX表达失调的模式已在各种癌症中被鉴定。同时,WT 1与HOXA 10基因密切相关,HOXA 10基因是一种诱导型转录因子。我们推测在卵巢癌的发病过程中,HOXA 10启动子CpG低甲基化与WT 1表达降低可能共同调节HOXA 10的表达。5-Aza-dC处理后,卵巢癌细胞系(SKOV-3和HEY)的HOXA 10表达显著增加。与对照siRNA转染相比,HOXA 10 siRNA转染SKOV-3和HEY卵巢癌细胞系显著下调HOXA 10表达,但上调WT 1表达。在卵巢癌样本中,HOXA 10表达显著高。而HOXA 10在正常乳腺组织中的表达较低(P
HOXA10 plays an important role in the body structure and development. Recently, patterns of deregulated HOX expression have been identified in various cancers. Meanwhile, WT1 is closely associated with the HOXA10 gene, which is an inducible transcription factor. We hypothesized that during the process of the ovarian cancer pathogenesis, the HOXA10 promoter CpG hypomethylation coupled with decreased WT1 expression could co-regulate HOXA10 expression. After the treatment of 5-Aza-dC, ovarian cancer cell lines(SKOV-3 and HEY) significantly increased HOXA10 expression. Transfection of HOXA10 siRNA with SKOV-3 and HEY ovarian cancer cell lines significantly downregulated HOXA10 expression but upregulated WT1 expression, compared to the control siRNA transfection. In ovarian cancer samples, the HOXA10 expression is significantly high. Nevertheless, the expression of HOXA10 is low in normal ones(P