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The Nedd8-activating enzyme inhibitor MLN4924 (TAK-924/Pevonedistat) induces apoptosis via c-Myc-Noxa axis in head and neck squamous cell carcinoma 期刊论文

编号：

6223fd4b-bc93-4ec9-8a10-af77af32d5a7
作者：

Zhang, Wenjuan#^[1,2]Liang, Yupei^[1];Li, Lihui^[1];Wang, Xiaofang^[1];Yan, Zi^[1];Dong, Changsheng^[2];Zeng, MuSheng^[3];Zhong, Qian^[3];Liu, XueKui^[4];Yu, Jinha^[5];Sun, Shuyang^[6];Liu, Xiaojun^[1];Kang, Jihui^[2];Zhao, Hu^[7];Jeong, Lak Shin*^[5]Zhang, Yanmei*^[7]Jia, Lijun*^[1,2]
语种：

英文
期刊：

CELL PROLIFERATION ISSN：0960-7722 2019 年 52 卷 2 期 ; MAR
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摘要：

Objectives The present study aimed to reveal expression status of the neddylation enzymes in HNSCC and to elucidate the anticancer efficacy and the underlying mechanisms of inhibiting neddylation pathway. Materials and methods The expression levels of neddylation enzymes were estimated by Western blotting in human HNSCC specimens and bioinformatics analysis of the cancer genome atlas (TCGA) database. Cell apoptosis was evaluated by Annexin V fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) stain and fluorescence-activated cell sorting (FACS). Small interfering RNA (siRNA) and the CRISPR-Cas9 system were used to elucidate the underlying molecular mechanism of MLN4924-induced HNSCC apoptosis. Results Expression levels of NAE1 and UBC12 were prominently higher in HNSCC tissues than that in normal tissues. Inactivation of the neddylation pathway significantly inhibited malignant phenotypes of HNSCC cells. Mechanistic studies revealed that MLN4924 induced the accumulation of CRL ligase substrate c-Myc that transcriptionally activated pro-apoptotic protein Noxa, which triggered apoptosis in HNSCC. Conclusions These findings determined the over-expression levels of neddylation enzymes in HNSCC and revealed novel mechanisms underlying neddylation inhibition induced growth suppression in HNSCC cells, which provided preclinical evidence for further clinical evaluation of neddylation inhibitors (eg, MLN4924) for the treatment of HNSCC.
推荐引用方式
GB/T 7714：

Zhang Wenjuan,Liang Yupei,Li Lihui, et al. The Nedd8-activating enzyme inhibitor MLN4924 (TAK-924/Pevonedistat) induces apoptosis via c-Myc-Noxa axis in head and neck squamous cell carcinoma [J].CELL PROLIFERATION,2019,52(2).
APA：

Zhang Wenjuan,Liang Yupei,Li Lihui,Wang Xiaofang,&Jia Lijun.(2019).The Nedd8-activating enzyme inhibitor MLN4924 (TAK-924/Pevonedistat) induces apoptosis via c-Myc-Noxa axis in head and neck squamous cell carcinoma .CELL PROLIFERATION,52(2).
MLA：

Zhang Wenjuan, et al. "The Nedd8-activating enzyme inhibitor MLN4924 (TAK-924/Pevonedistat) induces apoptosis via c-Myc-Noxa axis in head and neck squamous cell carcinoma" .CELL PROLIFERATION 52,2(2019).
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