p300 promotes proliferation, migration, and invasion via inducing epithelial-mesenchymal transition in non-small cell lung cancer cells.
p300 promotes proliferation, migration, and invasion via inducing epithelial-mesenchymal transition in non-small cell lung cancer cells.
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p300 通过诱导非小细胞肺癌细胞上皮间质转化促进增殖、迁移和侵袭
DOI：
10.1186/s12885-018-4559-3
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发表时间：
2018-06-07
期刊：
影响因子：
3.8
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Hou X;Gong R;Zhan J;Zhou T;Ma Y;Zhao Y;Zhang Y;Chen G;Zhang Z;Ma S;Chen X;Gao F;Hong S;Luo F;Fang W;Yang Y;Huang Y;Chen L;Yang H;Zhang L
组蛋白乙酰转移酶p300是一种重要的转录辅激活因子，在人类癌症中被认为是预后不良的因素。然而，p300在非小细胞肺癌增殖和远处转移中的实质性功能和机制尚不清楚。方法通过RNAi和重组质粒转染构建p300下调和上调细胞系。细胞计数试剂盒-8检测细胞增殖，菌落形成实验证实。采用伤口愈合试验和跨井室试验检测其迁移和侵袭能力。基于这些结果，我们在调节p300表达后测量上皮标记物和间质标记物，探讨p300促进NSCLC转移的上皮-间质转化的潜在机制。结果在NSCLC细胞NCI-H1975和NCI-H1993中，p300下调可抑制细胞增殖和集落形成。p300表达降低的细胞迁移和侵袭能力也受到抑制。相反，上调p300可显著增强NCI-H460的增殖、集落形成、迁移和侵袭能力。重要的是，进一步的研究表明，p300表达降低与间充质标志物表达减少和上皮标志物表达增加有关，而p300表达上调与上皮标志物表达减少和间充质标志物表达增加有关。结论p300是一种重要的肿瘤启动子，可促进非小细胞肺癌细胞的增殖、迁移和侵袭。上皮-间质转化是p300促进非小细胞肺癌转移的潜在机制。
BackgroundHistone acetyltransferase p300 is a crucial transcriptional coactivator and has been implicated as a poor prognostic factor in human cancers. However, little is known about the substantial functions and mechanisms of p300 in NSCLC proliferation and distant metastasis.MethodsWe constructed p300 down-regulated and up-regulated cell lines through RNAi and recombinant plasmid transfection. Cell Counting Kit-8 assays were used to test the cell proliferation and confirmed by colony formation assays. Wound healing assays and transwell chamber assays were used to test the migration and invasion ability. Based upon these results, we measured the epithelial markers and mesenchymal markers after regulating p300 expression to explore epithelial-mesenchymal transition as a potential mechanism of p300 promoting NSCLC metastasis.ResultsIn NSCLC cells NCI-H1975 and NCI-H1993, down-regulation of p300 leads to inhibition of cell proliferation and colony formation. Cells with reduced p300 expression also demonstrate inhibited migration and invasion ability. Contrarily, up-regulation of p300 significantly enhanced the proliferation, colony formation, migration and invasion ability of NCI-H460. Importantly, further investigation shows that decreased p300 expression is associated with reduced expression of mesenchymal markers and increased expression of epithelial markers, while up-regulated p300 expression correlated with decreased expression of epithelial markers and increased expression of mesenchymal markers.ConclusionsAs a crucial tumor promoter, p300 promotes cell proliferation, migration, and invasion in NSCLC cells. Epithelial-mesenchymal transition is a potential mechanism of p300 promoting NSCLC metastasis.
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影响因子：
7.4
作者：
Li M;Luo RZ;Chen JW;Cao Y;Lu JB;He JH;Wu QL;Cai MY
通讯作者：
Cai MY
影响因子：
11.4
作者：
Wojciak, Jonathan M.;Martinez-Yamout, Maria A.;Wright, Peter E.
通讯作者：
Wright, Peter E.
Skp2 表达对可切除食管鳞状细胞癌的生存产生不利影响。
影响因子：
7.4
作者：
Liang Y;Hou X;Cui Q;Kang TB;Fu JH;Zhang LJ;Luo RZ;He JH;Zeng YX;Yang HX
通讯作者：
Yang HX
影响因子：
8.8
作者：
通讯作者：
--
DOI：
10.1073/pnas.0905469106
发表时间：
2009-11-17
影响因子：
11.1
作者：
Byun, Jung S.;Wong, Madeline M.;Gardner, Kevin
通讯作者：
Gardner, Kevin