VOPP1, a determinant of the sensitivity of non-small cell lung cancer cells to NAE inhibitors
文献类型：期刊论文
| 作者 | Xu, Ru-Jun1,2; Bao, Xu-Bin1,2; Miao, Ze-Hong1,2; He, Jin-Xue1,2 |
| 刊名 | EUROPEAN JOURNAL OF PHARMACOLOGY
 |
| 出版日期 | 2025-09-15 |
| 卷号 | 1003页码:12 |
| 关键词 | NAE inhibitor Sensitivity biomarker VOPP1 CDT1 |
| ISSN号 | 0014-2999 |
| DOI | 10.1016/j.ejphar.2025.177942 |
| 英文摘要 | The failure of phase III clinical trials on the NEDD8-activating enzyme (NAE) inhibitor, MLN4924, has increased the demand for sensitive biomarkers for efficient patient selection. To date, no validated sensitivity biomarkers for NAE inhibitors have been reported. The Cancer Genome Atlas data revealed that the vesicular overexpressed in cancer pro-survival protein 1 (VOPP1) was overexpressed in solid tumors, and its expression levels significantly affected the prognosis of patients with non-small cell lung cancer (NSCLC). Changes in VOPP1 levels via knockout, small interfering RNA interference, re-expression, and overexpression were positively correlated with NAE inhibitor sensitivity in both NSCLC cell lines and xenograft models. NAE inhibitors also impacted cell cycle arrest and apoptosis. Mechanistically, reduced VOPP1 expression transcriptionally downregulated the E2F transcription factor 1 (E2F1) levels, which further impeded the transcription of the chromatin licensing and DNA replication factor 1 (CDT1). Our data suggest that the VOPP1-E2F1-CDT1 axis regulates the NAE inhibitor sensitivity of NSCLC cells. Furthermore, our findings provide important insights for further evaluation of VOPP1 as a potential NAE inhibitor sensitivity biomarker in clinical settings. |
| WOS关键词 | ANTICANCER ACTIVITY ; MLN4924 ; ENZYME ; CONTRIBUTES ; RESISTANCE ; LIGASES ; GROWTH |
| 资助项目 | National Natural Science Foundation of China[82073875] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001571005700001 |
| 出版者 | ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/321504]  |
| 专题 | 国家级研究中心_原创新药研究全国重点实验室 |
| 通讯作者 | He, Jin-Xue |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Canc Res Ctr, State Key Lab Drug Res, 501 Haike Rd, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xu, Ru-Jun,Bao, Xu-Bin,Miao, Ze-Hong,et al. VOPP1, a determinant of the sensitivity of non-small cell lung cancer cells to NAE inhibitors[J]. EUROPEAN JOURNAL OF PHARMACOLOGY,2025,1003:12. |
| APA | Xu, Ru-Jun,Bao, Xu-Bin,Miao, Ze-Hong,&He, Jin-Xue.(2025).VOPP1, a determinant of the sensitivity of non-small cell lung cancer cells to NAE inhibitors.EUROPEAN JOURNAL OF PHARMACOLOGY,1003,12. |
| MLA | Xu, Ru-Jun,et al."VOPP1, a determinant of the sensitivity of non-small cell lung cancer cells to NAE inhibitors".EUROPEAN JOURNAL OF PHARMACOLOGY 1003(2025):12. |
入库方式： OAI收割
来源：上海药物研究所
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