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:C0023890 (
cirrhosis
)
42,195
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
A previous study reported that histone methyltransferase
SETD3
is up-regulated in tumor tissues of hepatocellular carcinoma (HCC) and is associated with the growth of HCC. However, the clinical significance and the effect of
SETD3
on HCC metastasis remain unclear. In the present study, both the protein and mRNA expression levels of
SETD3
were measured in a larger cohort of HCC patients. The results showed that the protein level of
SETD3
in HCC tissues was significantly higher than that in non-tumorous tissues, which was inconsistent with the mRNA expression level of
SETD3
. The high protein level of
SETD3
in HCC tissues was significantly associated with male gender, poor pathological differentiation,
liver cirrhosis
and unfavorable prognosis of HCC patients. Subsequently, we demonstrated that
SETD3
could be regulated at post-transcriptional step by a couple of miRNAs (miR-16, miR-195 and miR-497). Additionally, in vitro and in vivo experiments revealed that
SETD3
played opposing roles in proliferation and metastasis of HCC: promoting proliferation but inhibiting metastasis. Mechanistic experiments revealed that doublecortin-like kinase 1 (DCLK1) was a downstream target of
SETD3
.
SETD3
could increase the DNA methylation level of DCLK1 promoter to inhibit the transcription of DCLK1. Further study revealed that DCLK1/PI3K/matrix metalloproteinase (MMP) 2 (MMP-2) was an important pathway that mediated the effect of
SETD3
on HCC metastasis. In conclusion, the present study revealed that
SETD3
is associated with tumorigenesis and is a promising biomarker for predicting the prognosis of HCC patients after surgical resection. In addition,
SETD3
plays inhibitory role in HCC metastasis partly through DCLK1/PI3K/MMP-2 pathway.
...
PMID:SETD3 is regulated by a couple of microRNAs and plays opposing roles in proliferation and metastasis of hepatocellular carcinoma. 3165 63
