RRC ID |
44787
|
著者 |
Shen Q, Yao Q, Sun J, Feng L, Lu H, Ma Y, Liu L, Wang F, Li J, Yue Y, Jin H, Wang X.
|
タイトル |
Downregulation of histone deacetylase 1 by microRNA-520h contributes to the chemotherapeutic effect of doxorubicin.
|
ジャーナル |
FEBS Lett
|
Abstract |
Doxorubicin induces DNA damage to exert its anti-cancer function. Histone deacetylase 1 (HDAC1) can protect the genome from DNA damage. We found that doxorubicin specifically downregulates HDAC1 protein expression and identified HDAC1 as a target of miR-520h, which was upregulated by doxorubicin. Doxorubicin-induced cell death was impaired by exogenous HDAC1 or by miR-520h inhibitor. Moreover, HDAC1 reduced the level of γH2AX by preventing the interaction of doxorubicin with DNA. In summary, doxorubicin downregulates HDAC1 protein expression, by inducing the expression of HDAC1-targeting miR-520h, to exacerbate DNA-doxorubicin interaction. The upregulation of HDAC1 protein may contribute to drug resistance of human cancer cells and targeting HDAC1 is a promising strategy to increase the clinical efficacy of DNA damage-inducing chemotherapeutic drugs.
|
巻・号 |
588(1)
|
ページ |
184-91
|
公開日 |
2014-1-3
|
DOI |
10.1016/j.febslet.2013.11.034
|
PII |
S0014-5793(13)00878-8
|
PMID |
24316511
|
MeSH |
Antibiotics, Antineoplastic / pharmacology
Blotting, Western
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
Cell Survival / genetics
DNA Damage
Dose-Response Relationship, Drug
Down-Regulation / drug effects*
Doxorubicin / pharmacology*
Gene Expression Regulation, Neoplastic / drug effects
Histone Deacetylase 1 / genetics*
Histone Deacetylase 1 / metabolism
Humans
MicroRNAs / genetics*
Reverse Transcriptase Polymerase Chain Reaction
Stomach Neoplasms / genetics
Stomach Neoplasms / metabolism
Stomach Neoplasms / pathology
Transcription, Genetic / drug effects
|
IF |
3.057
|
引用数 |
14
|
WOS 分野
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
リソース情報 |
ヒト・動物細胞 |
MKN45(RCB1001
MKN28(RCB1000) |