HMGN4 plays a key role in STAT3-mediated oncogenesis of triple-negative breast cancer
文献类型：期刊论文
| 作者 | Mou, Jiahui2,3; Xu, Xiaoding1; Wang, Feifei1; Kong, Weiwen2,3; Chen, Jing2,3 ; Ren, Jin2,3
|
| 刊名 | CARCINOGENESIS
 |
| 出版日期 | 2022-07-06 |
| 页码 | 11 |
| ISSN号 | 0143-3334 |
| DOI | 10.1093/carcin/bgac056 |
| 通讯作者 | Ren, Jin(jren@cdser.simm.ac.cn) |
| 英文摘要 | In this study, we revealed that HMGN4 regulated the proliferation of TNBC though STAT3 signaling, which indicated that HMGN4 was likely to be a potential novel target for anti-TNBC therapy. High-mobility group nucleosome-binding domain 4 (HMGN4) exerts biological functions by regulating gene transcription through binding with nucleosome. As a new epigenetic regulator discovered in 2001, its biological functions have not been clarified. HMGN4 belongs to HMGNs family, in which HMGN1, 2 and 5 have been reported to play roles in oncogenesis of various cancers. However, it is reported that HMGN4 was associated with thyroid and liver cancer. In this study, we discovered for the first time that HMGN4 was highly expressed in human triple-negative breast cancer (TNBC), based on the analysis of the TCGA database. Moreover, we found that HMGN4 controlled the proliferation of human TNBC cells both in vitro and in vivo. Mechanistically, the positive correlation occurred between HMGN4 and STAT3 downstream genes while HMGN4 played an indispensable role in constitutively active STAT3 (STAT3C) induced colony formation. Interestingly, we reported that STAT3 regulated HMGN4 transcription as its transcriptional factor by chromatin immunoprecipitation and HMGN4 promoter-luc assays. That is to say, there is a feed-forward signaling circuit between HMGN4 and STAT3, which might control TNBC cell growth. Finally, we proved that the interference of HMGN4 by nanovehicle-packaged siRNA may be a potentially effective approach in TNBC treatment. In summary, our findings not only identified a novel regulator in TNBC cell proliferation but also revealed the mechanism by which HMGN4 acted as a downstream gene of STAT3 to participate in the STAT3 pathway, which indicated that HMGN4 was likely to be a potential novel target for anti-TNBC therapy. |
| WOS关键词 | CONSTITUTIVE ACTIVATION ; STAT3 ; EXPRESSION ; OVEREXPRESSION ; INHIBITION ; MIGRATION ; INVASION |
| 资助项目 | Fundamental Research Funds for the State Key Laboratory of Drug Research[SIMM2103ZZ-01] ; Foundation of Shanghai Science and Technology Committee[21DZ2291100] ; Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine[ZYYCXTD-D-202210] |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000843712400001 |
| 出版者 | OXFORD UNIV PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/302290]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Ren, Jin |
| 作者单位 | 1.Nanjing Univ Chinese Med, Nanjing 210023, Peoples R China 2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 3.Chinese Acad Sci, Ctr Drug Safety Evaluat & Res, Shanghai Inst Mat Med, State Key Lab Drug Res, 501 Haike Rd, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Mou, Jiahui,Xu, Xiaoding,Wang, Feifei,et al. HMGN4 plays a key role in STAT3-mediated oncogenesis of triple-negative breast cancer[J]. CARCINOGENESIS,2022:11. |
| APA | Mou, Jiahui,Xu, Xiaoding,Wang, Feifei,Kong, Weiwen,Chen, Jing,&Ren, Jin.(2022).HMGN4 plays a key role in STAT3-mediated oncogenesis of triple-negative breast cancer.CARCINOGENESIS,11. |
| MLA | Mou, Jiahui,et al."HMGN4 plays a key role in STAT3-mediated oncogenesis of triple-negative breast cancer".CARCINOGENESIS (2022):11. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。