BPTF inhibition antagonizes colorectal cancer progression by transcriptionally inactivating Cdc25A
文献类型：期刊论文
| 作者 | Guo, Ping8; Zu, Shijia5,6; Han, Shilong8; Yu, Wendan8; Xue, Guoqing8; Lu, Xiaona8; Lin, Hua6; Zhao, Xinrui8; Lu, Haibo4,6; Hua, Chunyu8 |
| 刊名 | REDOX BIOLOGY
 |
| 出版日期 | 2022-09-01 |
| 卷号 | 55页码:16 |
| ISSN号 | 2213-2317 |
| 关键词 | Colorectal cancer BPTF Cdc25A c-Myc Cell cycle |
| DOI | 10.1016/j.redox.2022.102418 |
| 通讯作者 | Deng, Wuguo(dengwg@sysucc.org.cn) ; Luo, Cheng(cluo@simm.ac.cn) ; Guo, Wei(wei1015@dmu.edu.cn) |
| 英文摘要 | As the largest subunit of the nuclear remodeling factor complex, Bromodomain PHD Finger Transcription Factor (BPTF) has been reported to be involved in tumorigenesis and development in several cancers. However, to date, its functions and related molecular mechanisms in colorectal cancer (CRC) are still poorly defined and deserve to be revealed. In this study, we uncovered that, under the expression regulation of c-Myc, BPTF promoted CRC progression by targeting Cdc25A. BPTF was found to be highly expressed in CRC and promoted the proliferation and metastasis of CRC cells through BPTF specific siRNAs, shRNAs or inhibitors. Based on RNA-seq, combined with DNA-pulldown, ChIP and luciferase reporter assay, we proved that, by binding to-178/+107 region within Cdc25A promoter, BPTF transcriptionally activated Cdc25A, thus accelerating the cell cycle process of CRC cells. Meanwhile, BPTF itself was found to be transcriptionally regulated by c-Myc. Moreover, BPTF knockdown or inactivation was verified to sensitize CRC cells to chemotherapeutics, 5-Fluorouracil (5FU) and Oxaliplatin (Oxa), c-Myc inhibitor and cell cycle inhibitor not just at the cellular level in vitro, but in subcutaneous xeno-grafts or AOM/DSS-induced in situ models of CRC in mice, while Cdc25A overexpression partially reversed BPTF silencing-caused tumor growth inhibition. Clinically, BPTF, c-Myc and Cdc25A were highly expressed in CRC tissues simultaneously, the expression of any two of the three was positively correlated, and their expressions were highly relevant to tumor differentiation, TNM staging and poor prognosis of CRC patients. Thus, our study indicated that the targeted inhibition of BPTF alone, or together with chemotherapy and/or cell cycle-targeted therapy, might act as a promising new strategy for CRC treatment, while c-Myc/BPTF/Cdc25A signaling axis is expected to be developed as an associated set of candidate biomarkers for CRC diagnosis and prognosis prediction. |
| WOS关键词 | CELL-CYCLE PHOSPHATASE ; PHD-FINGER ; HEPATOCELLULAR-CARCINOMA ; EXPRESSION ; COMPLEXES ; THERAPY ; COLON ; PROLIFERATION ; GROWTH |
| 资助项目 | National Natural Science Foundation of China[82072711] ; National Natural Science Foundation of China[81772975] ; National Natural Science Foundation of China[81821005] ; National Natural Science Foundation of China[91853205] ; Scientific Research Fund project of Education Department of Liaoning Province-Service local project[LZ2020005] ; Liaoning Bai-Qian-Wan Talents Program, and LiaoNing Revitalization Talents Prograrn[XLYC2007172] ; National Key R&D Program of China[2021ZD0203900] |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| 出版者 | ELSEVIER |
| WOS记录号 | WOS:000877664700003 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/302873]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Deng, Wuguo; Luo, Cheng; Guo, Wei |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China 2.Sun Yat Sen Univ, Canc Ctr, Guangzhou, Peoples R China 3.Dalian Med Univ, Dalian, Peoples R China 4.Fudan Univ, Sch Pharm, 826 Zhangheng Rd, Shanghai 201203, Peoples R China 5.China Univ Chinese Acad Sci, Beijing 100049, Peoples R China 6.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 7.Sun Yat sen Univ Canc Ctr, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China, Canc Ctr, Guangzhou 510060, Peoples R China 8.Dalian Med Univ, Inst Canc Stem Cells, Dalian 116044, Peoples R China |
| 推荐引用方式 GB/T 7714 | Guo, Ping,Zu, Shijia,Han, Shilong,et al. BPTF inhibition antagonizes colorectal cancer progression by transcriptionally inactivating Cdc25A[J]. REDOX BIOLOGY,2022,55:16. |
| APA | Guo, Ping.,Zu, Shijia.,Han, Shilong.,Yu, Wendan.,Xue, Guoqing.,...&Guo, Wei.(2022).BPTF inhibition antagonizes colorectal cancer progression by transcriptionally inactivating Cdc25A.REDOX BIOLOGY,55,16. |
| MLA | Guo, Ping,et al."BPTF inhibition antagonizes colorectal cancer progression by transcriptionally inactivating Cdc25A".REDOX BIOLOGY 55(2022):16. |
入库方式： OAI收割
来源：上海药物研究所
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