A potential diagnostic marker for ovarian cancer: Involvement of the histone acetyltransferase, human males absent on the first.
A potential diagnostic marker for ovarian cancer: Involvement of the histone acetyltransferase, human males absent on the first.
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DOI：
10.3892/ol.2013.1380
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发表时间：
2013-08
期刊：
影响因子：
2.9
通讯作者：
Jin J
中科院分区：
文献类型：
--
作者：
Liu N;Zhang R;Zhao X;Su J;Bian X;Ni J;Yue Y;Cai Y;Jin J
人类雄性缺失的第一个(HMOF)是人类果蝇MOF蛋白的同源基因，负责人类细胞中组蛋白H4赖氨酸16(H4K16)的乙酰化。HMOF的缺失导致人类细胞组蛋白H4K16乙酰化水平的整体降低、基因组不稳定、细胞周期缺陷、某些基因转录减少、DNA损伤修复缺陷和早期胚胎死亡。研究表明，hMOF基因的异常表达与许多原发癌有关。本研究检测了hMOF表达和组蛋白H4K16乙酰化在临床诊断的原发卵巢癌组织中的作用。临床诊断为卵巢癌的冰冻组织用于聚合酶链式反应(PCR)、定量聚合酶链式反应(QPCR)、免疫印迹和免疫组织化学染色。对47例HMOF基因表达的聚合酶链式反应分析显示，81%的患者hMOF基因表达下调，而只有13%的患者表达上调。应用定量聚合酶链式反应(QPCR)验证hMOF在卵巢癌组织中的表达频繁下调。正如预期的那样，对57个样本的hMOF表达的分析显示，65%的患者hMOF mRNA表达显著下调(>；2倍下降)，而10.5%的患者hMOF表达下降2倍。此外，hMOF调节的人类白细胞抗原复合体5(HCP5)的表达在hMOF降低的患者中也被发现下调了87%。HMOF及其调控基因HCP5在卵巢癌中表达下调，提示hMOF可能参与了卵巢癌的发病机制。
Human males absent on the first (hMOF), a human ortholog of the Drosophila MOF protein, is responsible for histone H4 lysine 16 (H4K16) acetylation in human cells. The depletion of hMOF leads to a global reduction in histone H4K16 acetylation in human cells, genomic instability, cell cycle defects, reduced transcription of certain genes, defective DNA damage repair and early embryonic lethality. Studies have shown that abnormal hMOF gene expression is involved in a number of primary cancers. The present study examined the involvement of hMOF expression and histone H4K16 acetylation in clinically diagnosed primary ovarian cancer tissues. Clinically diagnosed frozen primary ovarian cancer tissues were used for polymerase chain reaction (PCR), quantitative PCR (qPCR), western blotting and immunohistochemical staining approaches. A PCR analysis of mRNA expression in 47 samples revealed a downregulation of hMOF mRNA in 81% of patients, whereas only 13% of patients demonstrated upregulation. qPCR was used to validate the frequent downregulation of hMOF expression in the primary ovarian cancer tissues. As expected, the analysis of hMOF expression in 57 samples revealed that hMOF mRNA expression was significantly downregulated (>2-fold decrease) in 65% of patients, while a <2-fold reduction of hMOF was observed in 10.5% of patients. Furthermore, the expression of hMOF-regulated human leukocyte antigen (HLA) complex 5, (HCP5), was also found to be downregulated in >87% of patients with a decrease in hMOF. hMOF and its regulated gene, HCP5, are frequently downregulated in human ovarian cancer, suggesting that hMOF may be involved in the pathogenesis of the disease.
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