MacroH2A suppresses the proliferation of the B16 melanoma cell line
MacroH2A suppresses the proliferation of the B16 melanoma cell line
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DOI：
10.3892/mmr.2014.2482
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发表时间：
2014-10-01
影响因子：
3.4
通讯作者：
Li, Jiaguang
中科院分区：
文献类型：
--
作者：
Lei, Shaorong;Long, Jianhong;Li, Jiaguang
MacroH2A是最常改变的组蛋白，其参与癌症进展。越来越多的证据表明，macroH2A可以通过影响细胞周期来调节癌症的进展。在本研究中，证明了macroH2A抑制黑色素瘤细胞的进展，并检查了这一过程的分子机制。构建macroH2A的干扰和过表达载体，转染B16黑色素瘤细胞，通过定量聚合酶链反应（PCR）、免疫印迹和免疫荧光分析进行分析。检测各组细胞凋亡及细胞周期。通过检测细胞周期蛋白D1、D3、细胞周期蛋白依赖性蛋白激酶4（cyclin-dependent protein kinase，CDK）4、CDK 6和CDK 8的表达，探讨macroH2A对细胞周期相关基因的影响。结果表明，macroH2A的过表达抑制了黑素瘤细胞的进展，并将细胞阻滞在G2/M期。此外，macroH2A抑制B16黑素瘤细胞中的细胞周期蛋白D1、细胞周期蛋白D2、CDK6和CDK8表达。总之，结果表明，macroH2A，染色质的关键组分，通过调节细胞周期蛋白D1，细胞周期蛋白D3和CDK6基因抑制黑色素瘤的发展（这是由细胞周期紊乱引起的）。
MacroH2A is the most frequently altered histone, which participates in cancer progression. Increasing evidence demonstrates that cancer progression could be regulated by macroH2A by affecting the cell cycle. In the present study, it was demonstrated that macroH2A suppresses melanoma cell progression and the molecular mechanisms underlying this process were examined. The interference and overexpression vectors of macroH2A were constructed and then transferred into B16 melanoma cells and, following transfection, were analyzed by quantitative polymerase chain reaction (PCR), western blot analysis and immunofluorescence assays. Apoptosis and the cell cycle stage among all the treatment groups were detected.. Then, cyclin D1, cyclin D3, cyclin-dependent protein kinase (CDK) 4, CDK6 and CDK8 expression was detected in order to elucidate the effects of macroH2A on cell cycle-related genes. The results demonstrated that the overexpression of macroH2A suppressed melanoma cell progression and arrested the cells in the G2/M stage. Furthermore, macroH2A inhibits cyclin D1, cyclin D2, CDK6 and CDK8 expression in B16 melanoma cells. In conclusion, the results demonstrated that macroH2A, a critical component of chromatin, suppresses the development of melanoma (which results from a disordered cell cycle) through regulating cyclin D1, cyclin D3 and CDK6 genes.