Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.1.1.37 (
DNA methyltransferase
)
4,983
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Sorafenib resistance and tumor metastasis account for poor outcome of hepatocellular carcinoma (HCC).
Histone deacetylase 11
(
HDAC11
) has been reported to exert oncogenic effects in several types of human cancer, but its specific functions and detailed mechanisms in HCC are not fully elucidated. Here we identified
HDAC11
as a potential oncogene and promising biomarker in HCC by
in silico
analysis.
Histone deacetylase 11
was upregulated in sorafenib-resistant SMMC7721 compared with its parental cell. Knockdown of
HDAC11
suppressed proliferation and sorafenib resistance, which may be due to inhibition of drug metabolism cytochrome P450 predicted by gene-set enrichment analysis. Histone deacetylase expression was higher in highly metastatic MHCC97H than lowly metastatic MHCC97L. Downregulation of
HDAC11
significantly attenuated the migrated and invaded abilities of HCC cells.
Histone deacetylase 11
was directly targeted and suppressed by miR-145-5p. Inhibition of miR-145-5p enhanced sorafenib resistance and metastasis of HCC, and these effects could be attenuated by knockdown of
HDAC11
. The promoter methylation level of
HDAC11
was markedly decreased in HCC tissues compared with normal controls. Administration of 5'-Aza-2'-deoxycytidine, a
DNA methyltransferase
inhibitor, facilitated
HDAC11
expression in HCC cells. Our data indicate a role of miR-145-5p/
HDAC11
axis in regulation of sorafenib resistance and metastasis in HCC.
...
PMID:Promoter Hypomethylation and miR-145-5p Downregulation- Mediated HDAC11 Overexpression Promotes Sorafenib Resistance and Metastasis of Hepatocellular Carcinoma Cells. 3290 37
