KDM3B suppresses APL progression by restricting chromatin accessibility and facilitating the ATRA-mediated degradation of PML/RAR alpha
文献类型：期刊论文
| 作者 | Wang, Xinrui1; Fan, Huiyong1; Xu, Congling1; Jiang, Guojuan1; Zhang, Ji1; Wang, Haiwei2,3; , |
| 刊名 | CANCER CELL INTERNATIONAL
 |
| 出版日期 | 2019 |
| 卷号 | 19期号:1页码:256 |
| 关键词 | KDM3B APL PML RAR alpha me2 Chromatin accessibility Differentiation |
| ISSN号 | 2045-2322 |
| DOI | 10.1186/s12935-019-0979-7 |
| 文献子类 | Article |
| 英文摘要 | Background A hallmark of acute promyelocytic leukemia (APL) is the expression of PML/RAR alpha fusion protein. Treatment with all-trans retinoic acid (ATRA) results in the terminal differentiation of neutrophil granulocytes. However, the underlying mechanisms remain largely unknown. Here, we identify and elucidate a novel differentiation-suppressive model of APL involving the histone demethylase KDM3B, which has been identified as a suppressor of the tumor genes involved in hematopoietic malignancies. Methods First, we established a KDM3B knockdown NB4 cell model to determine the functional characteristics of KDM3B by cell proliferation assay and flow cytometry. Then, we performed ChIP-seq and ATAC-seq to search for potential relationships among KDM3B, histone modification (H3K9me1/me2) and the chromatin state. Finally, molecular biological techniques and a multi-omics analysis were used to explore the role of KDM3B in differentiation of the leukemia cells after ATRA treatment. Results We found that knocking down KDM3B contributed to the growth of NB4 APL cells via the promotion of cell-cycle progression and blocked granulocytic differentiation. Through global and molecular approaches, we provided futher evidence that knocking down KDM3B altered the global distribution of H3K9me1/me2 and increased the chromatin accessibility. Moreover, knocking down KDM3B inhibited the ATRA-induced degradation of the PML/RAR alpha oncoprotein. Conclusion Our study suggested that KDM3B was able to inhibit APL progression by maintaining chromatin in a compact state and facilitating the ATRA-mediated degradation of PML/RAR alpha. Taken together, the results show that KDM3B may be an alternative target for the treatment regimens and the targeted therapy for APL by sustaining the function of PML/RAR alpha fusion protein. |
| 学科主题 | Science & Technology - Other Topics |
| WOS关键词 | TRANSCRIPTION FACTOR ; MYELOID-LEUKEMIA ; GENE-EXPRESSION ; DELETED REGION ; HISTONE ; LANDSCAPE ; IDENTIFICATION ; DEMETHYLASES ; CHROMOSOME-5 ; INTERPLAY |
| 语种 | 英语 |
| CSCD记录号 | CSCD:31592194 |
| WOS记录号 | WOS:000488958400001 |
| 出版者 | BMC |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/1198]  |
| 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.Shanghai Jiao Tong Univ, Sch Med, Rui Jin Hosp, State Key Lab Med Genom,Shanghai Inst Hematol, Shanghai 200025, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Shanghai 200025, Peoples R China; 3.Chinese Acad Sci, Grad Sch, Shanghai 200025, Peoples R China, |
| 推荐引用方式 GB/T 7714 | Wang, Xinrui,Fan, Huiyong,Xu, Congling,et al. KDM3B suppresses APL progression by restricting chromatin accessibility and facilitating the ATRA-mediated degradation of PML/RAR alpha[J]. CANCER CELL INTERNATIONAL,2019,19(1):256. |
| APA | Wang, Xinrui.,Fan, Huiyong.,Xu, Congling.,Jiang, Guojuan.,Zhang, Ji.,...&,.(2019).KDM3B suppresses APL progression by restricting chromatin accessibility and facilitating the ATRA-mediated degradation of PML/RAR alpha.CANCER CELL INTERNATIONAL,19(1),256. |
| MLA | Wang, Xinrui,et al."KDM3B suppresses APL progression by restricting chromatin accessibility and facilitating the ATRA-mediated degradation of PML/RAR alpha".CANCER CELL INTERNATIONAL 19.1(2019):256. |
入库方式： OAI收割
来源：上海营养与健康研究所
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