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:C0019204 (
hepatocellular carcinoma
)
71,386
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Liver cancer is one of the most common types of cancer among human malignancies.
Four and a half LIM domains 1
(
FHL1
), as a tumor suppressor gene, is frequently downregulated in multiple types of human cancer. However, the role and specific mechanisms of
FHL1
as a tumor suppressor in liver cancer are poorly understood. The present study aimed to investigate the role and associated mechanisms of
FHL1
in human liver cancer. The level of
FHL1
mRNA in
hepatocellular carcinoma
(
HCC
) tissue specimens and cell lines derived from the human liver was determined using reverse transcription polymerase chain reaction and western blot analysis. The association between
FHL1
expression and clinicopathological characteristics of patients with liver cancer was analyzed. Western blotting, small interfering RNA (siRNA) and chromatin immunoprecipitation were used to study the expression association of
FHL1
and enhancer of zeste homolog 2 (EZH2) in human liver cancer and to explore the regulatory mechanism of
FHL1
downregulation. Colony formation and migration assays were performed while
FHL1
was overexpressed in Hep3B cells. The results showed that the expression of
FHL1
mRNA in tumor tissue decreased, exhibiting a significant difference compared with the adjacent non-cancerous tissue (P<0.05). However, the downregulation of
FHL1
was not significantly associated with the sex, age, hepatitis B virus infection status, tumor size, distant metastasis status or level of tumor differentiation of the patients.
FHL1
was synergistically silenced by DNA methylation and histone modification, and 3-deanzaneplanocin A (DZNep), an inhibitor of EZH2, which is a histone methyltransferase of the polycomb repressive complex 2, which catalyzes histone H3 lysine 27 tri-methylation (H3K27me3). A significant association between
FHL1
and EZH2 expression was identified in the female
hepatocellular carcinoma
(
HCC
) samples, but was not in the male
HCC
samples.
FHL1
overexpression and DZNep treatment significantly suppressed the growth and migration of Hep3B cells by restoring
FHL1
expression. H3K27me3 was significantly enriched at the
FHL1
promoter region, as indicated by a chromatin immunoprecipitation assay, and associated with the epigenetic repression of the
FHL1
tumor suppressor gene in
HCC
cell lines. In conclusion, the present study provides an insight into DNA methylation and EZH2-H3K27me3 epigenetic repression of
FHL1
in human liver cancer.
...
PMID:Epigenetic analysis of FHL1 tumor suppressor gene in human liver cancer. 2911 54
