Kdm1a promotes SCLC progression by transcriptionally silencing the tumor suppressor Rest
文献类型：期刊论文
| 作者 | Jin, Yujuan1,2; Ma, Dingailu2; Gramyk, Tobin2; Fang, Rui2; Shi, Yujiang Geno2; Guo, Chenchen1; Ji, Hongbin1; , |
| 刊名 | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
 |
| 出版日期 | 2019 |
| 卷号 | 515期号:1页码:214-221 |
| 关键词 | CELL LUNG-CANCER REPRESSOR DIFFERENTIATION |
| ISSN号 | 0006-291X |
| DOI | 10.1016/j.bbrc.2019.05.118 |
| 文献子类 | Article |
| 英文摘要 | Small cell lung carcinoma (SCLC) is one of the deadliest cancer types, with a 5-year survival rate less than 10%. Kdm1a/Lsd1 has recently been implicated as a potential therapeutic target for SCLC. However, the underlying molecular mechanism by which Kdm1a promotes the oncogenesis of SCLC has not been fully understood. Kdm1a is significantly elevated in most human SCLC specimens, whereas Rest, a tumor suppressor and neuronal repressive transcriptional factor, is typically inactivated. Knock-out of Kdm1a (Kdm1a-KO) in mouse SCLC cell lines resulted in the suppression of cell growth and soft agar colony formation. RNA-Seq analysis of the Kdm1a-KO cells revealed significant repression of a program of neuroendocrine signature genes, and conversely, a significant upregulation of a network of genes capable of inhibiting tumor cell growth. Rest was identified among the top 10 upregulated genes in Kdm1a-KO cells. The treatment of the SCLC cells with Kdm1a demethylase inhibitors resulted in a dramatic up regulation of Rest similar to the extent of that in Kdm1a-KO cells. Importantly, accompanying the restored expression of the SCLC signature genes, knock-out of Rest in Kdm1a-KO cells rescued the restricted cell growth and soft agar colony formation. Taken together, these novel findings show that Kdm1a is a key transcriptional repressor of Rest, and that suppression of SCLC progression by the targeted inhibition of Kdm1a depends on the reactivation of Rest, suggesting a new strategy for effective SCLC treatment by targeting the Kdm1a/Rest molecular pathway. Published by Elsevier Inc. |
| 学科主题 | Biochemistry & Molecular Biology ; Biophysics |
| WOS关键词 | Small cell lung carcinoma ; Kdm1a ; Rest |
| 语种 | 英语 |
| WOS记录号 | WOS:000471737500033 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/3567]  |
| 专题 | 生化所2019-2020年发文 |
| 作者单位 | 1.CAS Ctr Excellence Mol Cell Sci, Innovat Ctr Cell Signaling Network, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China, 2.Harvard Med Sch, Brigham & Women Hosp, Div Endocrinol, Boston, MA 02115 USA; |
| 推荐引用方式 GB/T 7714 | Jin, Yujuan,Ma, Dingailu,Gramyk, Tobin,et al. Kdm1a promotes SCLC progression by transcriptionally silencing the tumor suppressor Rest[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2019,515(1):214-221. |
| APA | Jin, Yujuan.,Ma, Dingailu.,Gramyk, Tobin.,Fang, Rui.,Shi, Yujiang Geno.,...&,.(2019).Kdm1a promotes SCLC progression by transcriptionally silencing the tumor suppressor Rest.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,515(1),214-221. |
| MLA | Jin, Yujuan,et al."Kdm1a promotes SCLC progression by transcriptionally silencing the tumor suppressor Rest".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 515.1(2019):214-221. |
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