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:3.6.3.44 (
P-glycoprotein
)
13,344
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
SMYD2
is a histone methyltransferase that has been reported to be an important epigenetic regulator. This study aims to investigate
SMYD2
as a prognostic indicator of clear cell renal cell carcinoma (ccRCC) and explore its role in tumorigenesis and multi-drug resistance.
Methods
: Tumor specimens, clinicopathologic information, and prognostic outcomes of 186 ccRCC patients from three hospitals in China were collected for
SMYD2
immunohistochemistry staining, Kaplan-Meier analysis, and Cox proportional hazards-regression analysis. MicroRNA (miRNA)-microarray profiling identified differentially expressed miRNAs in renal cancer cells subjected to
SMYD2
knockdown or treatment with the
SMYD2
inhibitor AZ505. The effects of
SMYD2
and candidate
SMYD2
-mediated miRNAs on renal cancer cell proliferation, migration, clonogenicity, and tumorigenicity were determined via cell-function assays and murine xenograft experiments. The half-inhibitory concentrations (IC
50
) of five antineoplastic drugs (cisplatin, doxorubicin, fluorouracil, docetaxel, and sunitinib) in AZ505-treated and control cells were calculated, and the effects of
SMYD2
inhibition on
P-glycoprotein
(P-gP) expression and multiple-drug resistance were verified.
Results
:
SMYD2
was overexpressed and acted as an oncogene in ccRCC. High
SMYD2
expression correlated with a high TNM stage (P = 0.007) and early tumor relapse (P = 0.032).
SMYD2
independently predicted a worse overall survival (P = 0.022) and disease-free survival (P = 0.048). AZ505 inhibited the binding of
SMYD2
to the miR-125b promoter region (based on chromatin immunoprecipitation assays) and suppressed ccRCC cell migration and invasion by inhibiting the
SMYD2
/miR-125b/DKK3 pathway.
SMYD2
and miR-125b inhibition acted synergistically with anticancer drugs via P-gP suppression in vitro and in vivo.
Conclusions
: These findings suggested that
SMYD2
plays an important role in ccRCC development and could be a potential biomarker for the treatment and prognosis of RCC.
...
PMID:Inhibition of SMYD2 suppresses tumor progression by down-regulating microRNA-125b and attenuates multi-drug resistance in renal cell carcinoma. 3175 3
