Department of Medical Oncology, Sun Yat-sen University Cancer Center, 651 East Dongfeng Road, 510060, Guangzhou City, Guangdong Province, People's Republic of China.
State Key Laboratory of Oncology in South China, Guangzhou City, Guangdong Province, People's Republic of China.
BMC Cancer. 2018 Jun 7;18(1):641. doi: 10.1186/s12885-018-4559-3.
Histone 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.
We 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.
In 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.
As 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.
组蛋白乙酰转移酶 p300 是一种关键的转录共激活因子，已被认为是人类癌症的预后不良因素。然而，p300 在非小细胞肺癌增殖和远处转移中的重要功能和机制知之甚少。
我们通过 RNAi 和重组质粒转染构建了 p300 下调和上调的细胞系。细胞计数试剂盒-8 测定用于检测细胞增殖，并通过集落形成测定进行验证。划痕愈合试验和 Transwell 室试验用于检测迁移和侵袭能力。基于这些结果，我们在调节 p300 表达后测量上皮标志物和间充质标志物，以探索上皮-间充质转化作为 p300 促进非小细胞肺癌转移的潜在机制。
在非小细胞肺癌细胞系 NCI-H1975 和 NCI-H1993 中，下调 p300 导致细胞增殖和集落形成受到抑制。p300 表达减少的细胞迁移和侵袭能力也受到抑制。相反，上调 p300 显著增强了 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 表达减少与间充质标志物表达减少和上皮标志物表达增加相关，而上调 p300 表达与上皮标志物表达减少和间充质标志物表达增加相关。
作为一种关键的肿瘤促进因子，p300 促进非小细胞肺癌细胞的增殖、迁移和侵袭。上皮-间充质转化是 p300 促进非小细胞肺癌转移的潜在机制。
