Abstract：
:Histone deacetylases (HDACs) can enzymatically transferred acetyl functional group from protein or lysine residues of histone, so they can regulate the expression of lots of genes. Now HDACs are used as drug targets and many HDAC inhibitors (HDACis) were approved for cancer therapy or in clinical trials. However, the physiological mechanisms and regulatory processes of HDACi anti-cancer effects are largely unexplored and uncompleted. Here we use the virtual screening workflow obtained 25 hit compounds and ZINC24469384 can significantly inhibit HDAC activity while arrest cell cycle at G1/S phase and significantly induced HepG2 cell apoptosis, time-course RNA-seq demonstrate that HepG2 cells transcriptionally respond to ZINC24469384. Pathway analysis of DEGs and DASGs reveal that NR1H4 may play an important role in ZINC24469384-induced anti-proliferation effect and is dramatically alleviated by down-regulating the SOCS2 expression and promoting STAT3 phosphorylation in knockdown NR1H4 HepG2 cells. Analysis based on TCGA database indicated that NR1H4 and SOCS2 were downregulated in liver cancer, this suggest NR1H4 and SOCS2 may play an important role in tumorigenesis. These results indicated that ZINC24469384 is a novel benzamine lead compound of HDACi and provides a novel mechanism for HDACi to inhibit cancer.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Song Q,Li M,Fan C,Liu Y,Zheng L,Bao Y,Sun L,Yu C,Song Z,Sun Y,Wang G,Huang Y,Li Ydoi
10.1038/s41598-019-39487-6subject
Has Abstractpub_date
2019-02-20 00:00:00pages
2350issue
1issn
2045-2322pii
10.1038/s41598-019-39487-6journal_volume
9pub_type
杂志文章abstract：:In this report, we demonstrate mid-infrared dual-waveband (i.e., ~3 μm and ~2 μm) pulses from a cascaded gain-switched Ho3+-doped ZBLAN fiber laser by the use of hybrid pumping of 1150 nm CW and pulse LDs for the first time. Stable ~3 μm gain-switched pulses with the maximum output power 262.14 mW and shortest pulse d...
journal_title：Scientific reports
pub_type： 杂志文章
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pub_type： 杂志文章
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更新日期：2017-02-20 00:00:00
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journal_title：Scientific reports
pub_type： 已发布勘误
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journal_title：Scientific reports
pub_type： 杂志文章
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pub_type： 杂志文章
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pub_type： 杂志文章
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pub_type： 杂志文章
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pub_type： 杂志文章
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pub_type： 杂志文章
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pub_type： 杂志文章
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journal_title：Scientific reports
pub_type： 杂志文章
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pub_type： 杂志文章
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journal_title：Scientific reports
pub_type： 杂志文章
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更新日期：2020-08-07 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
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更新日期：2017-11-16 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep11003
更新日期：2015-07-17 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep07147
更新日期：2014-11-21 00:00:00
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pub_type： 杂志文章
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pub_type： 杂志文章
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pub_type： 杂志文章
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更新日期：2016-01-21 00:00:00
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pub_type： 杂志文章
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更新日期：2016-05-25 00:00:00
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更新日期：2015-09-15 00:00:00
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journal_title：Scientific reports
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更新日期：2020-02-20 00:00:00
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pub_type： 杂志文章
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更新日期：2020-02-05 00:00:00
