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:2.4.2.30 (
PARP
)
13,611
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The role of
DHX15
, a newly identified DEAH-box RNA helicase, in leukemogenesis remains elusive. Here, we identified a recurrent mutation in
DHX15
(NM_001358:c.664C>G: p.(R222G)) in one familial AML patient and 4/240 sporadic AML patients. Additionally,
DHX15
was commonly overexpressed in AML patients and associated with poor overall survival (OS) (P=0.019) and relapse-free survival (RFS) (P=0.032). In addition, we found a distinct expression pattern of
DHX15
.
DHX15
was highly expressed in hematopoietic stem cells and leukemia cells but was lowly expressed in mature blood cells.
DHX15
was down-regulated when AML patients achieved disease remission or when leukemia cell lines were induced to differentiate.
DHX15
silencing greatly inhibited leukemia cell proliferation and induced cell apoptosis and G1-phase arrest. In contrast, the restoration of
DHX15
expression rescued cell viability and reduced cell apoptosis. In addition, we found that
DHX15
was down-regulated when cell apoptosis was induced by ATO (arsenic trioxide); overexpression of
DHX15
caused dramatic resistance to ATO-induced cell apoptosis, suggesting an important role for
DHX15
in cell apoptosis. We further explored the mechanism of
DHX15
in apoptosis and found that overexpression of
DHX15
activated
NF-kB
transcription. Knockdown of
DHX15
inhibited the nuclear translocation and activation of the NF-kB subunit P65 in leukemia cells. Several downstream targets of the NF-kB pathway were also down-regulated, and apoptosis-associated genes
CASP3
and
PARP
were activated. In conclusion, this study represents the first demonstration that
DHX15
plays an important role in leukemogenesis via the NF-kB signaling pathway and may serve as an independent prognostic marker for AML.
...
PMID:DHX15 is associated with poor prognosis in acute myeloid leukemia (AML) and regulates cell apoptosis via the NF-kB signaling pathway. 2916 77
