Transcriptomics,Genomics

Dataset Information

102

Inhibition of H3K4 demethylation induces autophagy in cancer cell lines


ABSTRACT: 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. Overall design: Examination of RNA from U2OS cell with 10 kinds of small molecules treatment

INSTRUMENT(S): Illumina HiSeq 2500 (Homo sapiens)

SUBMITTER: Pinji Lei  

PROVIDER: GSE89672 | GEO | 2017-11-07

SECONDARY ACCESSION(S): PRJNA352870

REPOSITORIES: GEO

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Publications

Inhibition of H3K4 demethylation induces autophagy in cancer cell lines.

Wang Zhen Z   Long Qiao-Yun QY   Chen Lin L   Fan Jia-Dong JD   Wang Zhao-Ning ZN   Li Lian-Yun LY   Wu Min M   Chen Xuefeng X  

Biochimica et biophysica acta. Molecular cell research 20170808 12


Epigenetic factors and related small molecules have emerged to be strongly involved in autophagy process. Here we report that 2-PCPA and GSK-LSD1, two inhibitors of histone H3K4 demethylase KDM1A/LSD1, induce autophagy in multiple mammalian cell lines. The two small molecules induce accumulation of LC3II, formation of autophagosome and autolysosome, and SQSTM1/p62 degradation. 2-PCPA treatment inhibits cell proliferation through cell cycle arrest but does not inducing cell death. Exogenous expre  ...[more]

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