RRC ID 44787
Author Shen Q, Yao Q, Sun J, Feng L, Lu H, Ma Y, Liu L, Wang F, Li J, Yue Y, Jin H, Wang X.
Title Downregulation of histone deacetylase 1 by microRNA-520h contributes to the chemotherapeutic effect of doxorubicin.
Journal 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.
Volume 588(1)
Pages 184-91
Published 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
Times Cited 14
WOS Category BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
Resource
Human and Animal Cells MKN45(RCB1001 MKN28(RCB1000)