Genome-wide analyses identify KLF4 as an important negative regulator in T-cell acute lymphoblastic leukemia through directly inhibiting T-cell associated genes
文献类型：期刊论文
| 作者 | Li Wei; Jiang Zhiwu; Li Tianzhong; Wei Xinru; Zheng Yi; Wu Donghai; Yang Lijian; Chen Shaohua; Xu Bing; Zhong Mei |
| 刊名 | MOLECULAR CANCER
 |
| 出版日期 | 2015 |
| 英文摘要 | Background: Kruppel-like factor 4 (KLF4) induces tumorigenesis or suppresses tumor growth in a tissue-dependent manner. However, the roles of KLF4 in hematological malignancies and the mechanisms of action are not fully understood. Methods: Inducible KLF4-overexpression Jurkat cell line combined with mouse models bearing cell-derived xenografts and primary T-cell acute lymphoblastic leukemia (T-ALL) cells from four patients were used to assess the functional role of KLF4 in T-ALL cells in vitro and in vivo. A genome-wide RNA-seq analysis was conducted to identify genes regulated by KLF4 in T-ALL cells. Chromatin immunoprecipitation (ChIP) PCR was used to determine direct binding sites of KLF4 in T-ALL cells. Results: Here we reveal that KLF4 induced apoptosis through the BCL2/BCLXL pathway in human T-ALL cell lines and primary T-ALL specimens. In consistence, mice engrafted with KLF4-overexpressing T-ALL cells exhibited prolonged survival. Interestingly, the KLF4-induced apoptosis in T-ALL cells was compromised in xenografts but the invasion capacity of KLF4-expressing T-ALL cells to hosts was dramatically dampened. We found that KLF4 overexpression inhibited T cell-associated genes including NOTCH1, BCL11B, GATA3, and TCF7. Further mechanistic studies revealed that KLF4 directly bound to the promoters of NOTCH1, BCL2, and CXCR4 and suppressed their expression. Additionally, KLF4 induced SUMOylation and degradation of BCL11B. Conclusions: These results suggest that KLF4 as a major transcription factor that suppresses the expression of T-cell associated genes, thus inhibiting T-ALL progression. |
| 收录类别 | SCI |
| 原文出处 | http://www.molecular-cancer.com/content/14/1/26 |
| 语种 | 英语 |
| 源URL | [http://ir.siat.ac.cn:8080/handle/172644/9160]  |
| 专题 | 深圳先进技术研究院_其他 |
| 作者单位 | MOLECULAR CANCER |
| 推荐引用方式 GB/T 7714 | Li Wei,Jiang Zhiwu,Li Tianzhong,et al. Genome-wide analyses identify KLF4 as an important negative regulator in T-cell acute lymphoblastic leukemia through directly inhibiting T-cell associated genes[J]. MOLECULAR CANCER,2015. |
| APA | Li Wei.,Jiang Zhiwu.,Li Tianzhong.,Wei Xinru.,Zheng Yi.,...&Li Peng.(2015).Genome-wide analyses identify KLF4 as an important negative regulator in T-cell acute lymphoblastic leukemia through directly inhibiting T-cell associated genes.MOLECULAR CANCER. |
| MLA | Li Wei,et al."Genome-wide analyses identify KLF4 as an important negative regulator in T-cell acute lymphoblastic leukemia through directly inhibiting T-cell associated genes".MOLECULAR CANCER (2015). |
入库方式： OAI收割
来源：深圳先进技术研究院
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。