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| Status |
Public on Nov 07, 2017 |
| Title |
Inhibition of H3K4 demethylation induces autophagy in cancer cell lines |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Epigenetic factors and related small molecules have emerged to be strongly involved in autophagy process. Here we report that two inhibitors of histone H3K4 demethylase KDM1A/LSD1, 2-PCPA and GSK-LSD1, are able to induce autophagy in multiple cell lines. The two small molecules induced accumulation of LC3II, formation of autophagosome, fusion of autophagosome with lysosome and SQSTM1/p62 degradation. 2-PCPA treatment inhibits cell proliferation through cell cycle arrest but not inducing cell death. Exogenous expression of KDM1A/LSD1 impaired the autophagic phenotypes triggered by 2-PCPA. The autophagy induced by 2-PCPA requires LC3-II processing machinery. But depletion of BECN1 and ULK1 with siRNA did not affect the LC3-II accumulation triggered by 2-PCPA. 2-PCPA treatment induces the change of global gene expression program, including a series of autophagy-related genes, such as SQSTM1/p62. Taken together, our data indicate that KDM1A/LSD1 inhibitors induce autophagy through affecting the expression of autophagy-related genes and in a BECN1-independent manner.
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| |
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| Overall design |
Examination of RNA from U2OS cell with 10 kinds of small molecules treatment
|
| |
|
| Contributor(s) |
Wang Z, Lei P |
| Citation(s) |
28800922 |
| |
| Submission date |
Nov 08, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Pin-Ji Lei |
| E-mail(s) |
leipinji@gmail.com
|
| Organization name |
Massachusetts General Hospital
|
| Department |
Department of Radiation Oncology
|
| Lab |
Edwin L. Steele Laboratories
|
| Street address |
100 Blossom Street
|
| City |
Boston |
| State/province |
Massachusetts |
| ZIP/Postal code |
02114 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
| Samples (14)
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| Relations |
| BioProject |
PRJNA352870 |
| SRA |
SRP092975 |
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