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: UMLS:C1864663 (
HCC
)
2,985
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The capability for DNA double-strand breaks (DSBs) repair is crucial for chromatin dramatic changes and DNA damage in normal and tumor cells. We have investigated the clinicopathological significance of DNA repair gene
Ku70
expression in hepatocellular carcinoma. We demonstrated that
Ku70
expression was significantly increased in
HCC
, and the high expression levels were significantly correlated with gender, maximal tumor size, HBsAg status, tumor nodule number, distant metastasis and Ki-67 expression by clinicopathological analysis. The Kaplan-Meier survival curves revealed that increasing
Ku70
expression was associated with poor prognosis in
HCC
patients.
Ku70
expression was an independent prognostic marker of overall
HCC
patient survival in a multivariate analysis. In addition, through serum starvation and refeeding, we found that
Ku70
was lowly expressed in serum-starved Huh7 and HepG2
HCC
cells, and was progressively increased after serum-additioning. Furthermore, knockdown of
Ku70
inhibited cell proliferation accompanying an increase in p27(kip1) levels through interacting with FOXO4. These findings provide a rational framework for the progression of
HCC
and could be a potential molecular therapy by targeting the
Ku70
-FOXO4 interaction.
...
PMID:The DNA damage repair protein Ku70 regulates tumor cell and hepatic carcinogenesis by interacting with FOXO4. 2679 21
SIRT6 is a class III histone deacetylase that has been implicated in
HCC
development. We previously reported that SIRT6 potentiated apoptosis evasion in hepatocellular carcinoma by inhibiting both Bax expression and mitochondrial translocalization. However, the mechanism underlying SIRT6-mediated inhibition of Bax mitochondrial localization remains elusive. In this study, we found that although SIRT6 had no effect on the expression level of
Ku70
, SIRT6 could interact with
Ku70
and deacetylate it. The increased acetylation of
Ku70
in SIRT6-depleted cells disrupt its interaction with Bax, which finally resulted in Bax mitochondrial translocalization. Furthermore, lysine K542 on
Ku70
was the target for deacetylation by SIRT6.
Ku70
K542Q
mutation abolished suppression of association between
Ku70
and Bax and caused redistribution of Bax to the cytosol in SIRT6-depleted cells. Finally,
Ku70
K542Q
mutation could reversed the inhibition of growth and apoptosis promotion mediated by SIRT6 silencing. Together, our findings revealed SIRT6 could block the mitochondrial translocation of Bax and decrease the apoptotic ratio of
HCC
cells by deacetylation of
Ku70
. SIRT6 may serve as a promising target for developing targeted therapies for
HCC
in the future.
...
PMID:Deacetylation of Ku70 by SIRT6 attenuates Bax-mediated apoptosis in hepatocellular carcinoma. 2823 84
