Liao Zhi-Wei, Zhao Lei, Cai Mu-Yan, Xi Mian, He Li-Ru, Yu Fang, Zhou Tong-Chong, Liu Meng-Zhong
Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China; Department of Radiation Oncology, The Tumour Hospital Affiliated of Guangzhou Medical University, Guangzhou, Guangdong 510095, P.R. China.
Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China.
Oncol Lett. 2017 Feb;13(2):763-769. doi: 10.3892/ol.2016.5491. Epub 2016 Dec 13.
A previous study demonstrated that p300 is overexpressed in nasopharyngeal carcinoma (NPC), and that its expression is an independent prognostic factor. The aim of the present study is to investigate the role of in human NPC development. A small hairpin (sh) RNA lentiviral expression vector targeting the gene was constructed to suppress the expression of p300 in NPC cells. Knockdown of was verified by reverse transcription-quantitative polymerase chain reaction and western blotting. Wound-healing, invasion, immunofluorescence and immunoprecipitation assays were performed to assess the influence of p300 on nasopharyngeal tumorigenesis and metastasis . The expression of p300 was upregulated in NPC cell lines. After knockdown of , the migration and invasion ability of shp300 cells were significantly inhibited (P<0.05). Furthermore, the depletion of p300 expression in NPC cell lines resulted in the upregulation of epithelial phenotype marker E-cadherin and α-catenin, and downregulation of mesenchymal phenotype markers N-cadherin and vimentin. p300 promotes epithelial-mesenchymal transition (EMT) through the acetylation of Smad2 and Smad3 in the tumor growth factor-β signaling pathway. In conclusion, p300 may be involved in the invasion and metastasis of NPC through the induction of EMT.
先前的一项研究表明,p300在鼻咽癌(NPC)中过表达,且其表达是一个独立的预后因素。本研究的目的是探讨p300在人类鼻咽癌发生发展中的作用。构建了靶向p300基因的小发夹(sh)RNA慢病毒表达载体,以抑制NPC细胞中p300的表达。通过逆转录-定量聚合酶链反应和蛋白质免疫印迹法验证了p300的敲低。进行了伤口愈合、侵袭、免疫荧光和免疫沉淀实验,以评估p300对鼻咽癌发生和转移的影响。p300在NPC细胞系中表达上调。敲低p300后,shp300细胞的迁移和侵袭能力显著受到抑制(P<0.05)。此外,NPC细胞系中p300表达的缺失导致上皮表型标志物E-钙黏蛋白和α-连环蛋白上调,间充质表型标志物N-钙黏蛋白和波形蛋白下调。p300通过肿瘤生长因子-β信号通路中Smad2和Smad3的乙酰化促进上皮-间质转化(EMT)。总之,p300可能通过诱导EMT参与NPC的侵袭和转移。