Investigation of the expression patterns and correlation of DNA methyltransferases and class I histone deacetylases in ovarian cancer tissues.
Investigation of the expression patterns and correlation of DNA methyltransferases and class I histone deacetylases in ovarian cancer tissues.
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DOI：
10.3892/ol.2012.1057
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发表时间：
2013-02
期刊：
影响因子：
2.9
通讯作者：
Shao Q
中科院分区：
文献类型：
--
作者：
Gu Y;Yang P;Shao Q;Liu X;Xia S;Zhang M;Xu H;Shao Q
近年来有研究报道DNA甲基转移酶（dnmt）和组蛋白去乙酰化酶（HDACs）参与肿瘤的表观遗传调控，并促进细胞增殖和肿瘤发生。这些机制在卵巢癌中也发挥重要作用，但关于dnmt和hdac在卵巢癌中的相关性知之甚少。本研究采用实时定量逆转录聚合酶链反应（qRT-PCR）和免疫组织化学染色技术检测了22例卵巢癌和8例正常卵巢组织中DNMTs和I类hdac mRNA和蛋白的表达情况。此外，我们评估了这些基因与临床病理分期和mRNA表达的相关性。结果显示，DNMT1、DNMT3b和I类hdac mRNA表达在卵巢癌中升高，而DNMT3a的表达在癌组织和正常卵巢中无差异。此外，免疫组化染色结果显示，DNMT1和DNMT3b在卵巢癌样本中显著升高。此外，DNMT1、DNMT3b、HDAC1和HDAC2在III/IV期卵巢癌中的表达明显高于I/II期。HDAC2的表达与HDCA1、HDAC3、HDAC8呈正相关，DNMT1与DNMT3b呈正相关。同时，DNMT3b与HDAC1、HDAC2相关。HDAC1可能上调dnmt的表达，但这需要体外和体内实验的证实。I类hdac、DNMT1和DNMT3b的总体高表达率表明，这些mrna应作为卵巢癌的预测因素进行探索。此外，HDAC1、HDAC2和DNMT3b共同控制卵巢癌的进展。确定HDACs和DNMTs在卵巢癌中的相关性，不仅可以进一步阐明HDACs和DNMTs的发生发展机制，还可以指导临床使用HDACs和DNMTs抑制剂进行治疗。
Recent studies have reported that DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) are involved in the epigenetic regulation of cancer, as well as promoting cell proliferation and tumorigenesis. These mechanisms also play important roles in ovarian cancer, but little is known concerning the correlation of DNMTs and HDACs in ovarian cancer. In the present study, we used quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemical staining to examine the mRNA and protein expression of DNMTs and class I HDACs of tissues from 22 cases of ovarian cancer and 8 normal ovaries as a control. Furthermore, we assessed the correlation with clinicopathological stages and the mRNA expression of these genes. The results indicated that the mRNA expression of DNMT1, DNMT3b and class I HDACs was increased in ovarian cancers, while the expression of DNMT3a was not different between cancer tissues and normal ovaries. Additionally, the results of immunohistochemical staining demonstrated that DNMT1 and DNMT3b were significantly increased in ovarian cancer samples. Furthermore, the expression of DNMT1, DNMT3b, HDAC1 and HDAC2 was significantly higher in stage III/IV compared with stage I/II ovarian carcinomas. The expression of HDAC2 was positively correlated with HDCA1, HDAC3 and HDAC8, and DNMT1 was positively correlated with DNMT3b. Simultaneously, DNMT3b was correlated with HDAC1 and HDAC2. HDAC1 may upregulate the expression of DNMTs, but this requires confirmation by in vitro and in vivo experiments. The overall high rate of expression for class I HDACs, DNMT1 and DNMT3b suggested that these mRNAs should be explored as predictive factors in ovarian cancer. In addition, HDAC1, HDAC2 and DNMT3b cooperated in controlling ovarian cancer progression. Determining the correlations between HDACs and DNMTs in ovarian cancer will not only further clarify the mechanisms of genesis and development, but also guide clinical therapy using the inhibitors of HDACs and DNMTs.
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影响因子：
13.5
作者：
Braconi, Chiara;Huang, Nianyuan;Patel, Tushar
通讯作者：
Patel, Tushar
影响因子：
5.6
作者：
Gregoretti, IV;Lee, YM;Goodson, HV
通讯作者：
Goodson, HV
DOI：
10.1067/s0002-9378(03)00579-9
发表时间：
2003-10-01
影响因子：
9.8
作者：
Barnholtz-Sloan, JS;Schwartz, AG;Munkarah, AR
通讯作者：
Munkarah, AR
影响因子：
2.2
作者：
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通讯作者：
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影响因子：
30.8
作者：
Fuks, F;Burgers, WA;Kouzarides, T
通讯作者：
Kouzarides, T