Epigenetic Regulation of NAMPT by NAMPT-AS Drives Metastatic Progression in Triple-Negative Breast Cancer
文献类型：期刊论文
| 作者 | Zhang, Hanwen1; Zhang, Ning1; Liu, Ying1; Liang, Yiran1; Li, Yaming1; Wang, Xiaolong1; Chen, Tong1; Song, Xiaojin1; Sang, Yuting1; Duan, Yi1 |
| 刊名 | CANCER RESEARCH
 |
| 出版日期 | 2019 |
| 卷号 | 79期号:13页码:3347-3359 |
| ISSN号 | 0008-5472 |
| DOI | 10.1158/0008-5472.CAN-18-3418 |
| 文献子类 | Article |
| 英文摘要 | Triple-negative breast cancer (TNBC) is highly heterogeneous and has a poor prognosis. It is therefore important to identify the underlying molecular mechanisms in order to develop novel therapeutic strategies. Although emerging research has revealed long noncoding RNAs (lncRNA) as vital to carcinogenesis and cancer progression, their functional involvement in TNBC has not been well defined. In this study, we utilized the The Cancer Genome Atlas (TCGA) database and analyzed clinical samples to show that the long noncoding antisense transcript of nicotinamide phosphoribosyltransferase (NAMPT), NAMPT-AS, is upregulated in TNBC and is associated with poor prognosis, lymph node involvement, metastasis, and advanced stage. NAMPT-AS was cotranscribed with NAMPT from a bidirectional promoter, where the distributions of H3K4me3 and H3K27Ac chromatin modifications were enriched based on ENCODE and FANTOM5, suggesting the potential enhancer-RNA characteristics of NAMPT-AS. NAMPT-AS epigenetically regulated the expression of NAMPT in two divergent ways: NAMPT-AS recruited POU2F2 to activate the transcription of NAMPT, and NAMPT-AS acted as a competing endogenous RNA to rescue NAMPT degradation from miR-548b-3p. NAMPT-AS/NAMPT promoted tumor progression and regulated autophagy through the mTOR pathway in vitro and in vivo. In a cohort of 480 breast cancer patients, NAMPT was associated with breast cancer-specific survival and overall survival. These results demonstrate that NAMPT-AS is an oncogenic lncRNA in TNBC that epigenetically activates NAMPT to promote tumor progression and metastasis. Furthermore, these data identify NAMPT-AS/NAMPT as promising therapeutic targets in patients with TNBC. Significance: Upregulation of the long noncoding antisense RNA of NAMPT gene (NAMPT-AS) is associated with metastasis and poor prognosis in TNBC. |
| 学科主题 | Oncology |
| WOS关键词 | GENE-EXPRESSION ; AUTOPHAGY ; TRANSCRIPTION ; APOPTOSIS ; RNA ; INHIBITION ; REVEALS ; PATHWAY ; MTORC1 ; LOCALIZATION |
| 语种 | 英语 |
| WOS记录号 | WOS:000473533400019 |
| 出版者 | AMER ASSOC CANCER RESEARCH |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/1245]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Shandong Univ, Qilu Hosp, Dept Breast Surg, Jinan, Shandong, Peoples R China; 2.Shandong Univ, Qilu Hosp, Dept Pathol, Jinan, Shandong, Peoples R China; 3.Shandong Univ, Qilu Hosp, Pathol Tissue Bank, Jinan, Shandong, Peoples R China; 4.Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada; 5.Shandong Univ, Sch Med, Dept Cell Biol, Jinan, Shandong, Peoples R China; 6.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Key Lab Stem Cell Biol, Shanghai, Peoples R China; 7.Shanghai Jiao Tong Univ, Sch Med, Univ Chinese Acad Sci, Shanghai, Peoples R China, |
| 推荐引用方式 GB/T 7714 | Zhang, Hanwen,Zhang, Ning,Liu, Ying,et al. Epigenetic Regulation of NAMPT by NAMPT-AS Drives Metastatic Progression in Triple-Negative Breast Cancer[J]. CANCER RESEARCH,2019,79(13):3347-3359. |
| APA | Zhang, Hanwen.,Zhang, Ning.,Liu, Ying.,Liang, Yiran.,Li, Yaming.,...&,.(2019).Epigenetic Regulation of NAMPT by NAMPT-AS Drives Metastatic Progression in Triple-Negative Breast Cancer.CANCER RESEARCH,79(13),3347-3359. |
| MLA | Zhang, Hanwen,et al."Epigenetic Regulation of NAMPT by NAMPT-AS Drives Metastatic Progression in Triple-Negative Breast Cancer".CANCER RESEARCH 79.13(2019):3347-3359. |
入库方式： OAI收割
来源：上海营养与健康研究所
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