Gene/Protein
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Drug
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Compound
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Gene/Protein
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Target Concepts:
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Query: UMLS:C0345904 (
liver cancer
)
15,188
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Intrahepatic cholangiocarcinoma (ICC) ranks as the second most malignant type of primary
liver cancer
with a high degree of incidence and a very poor prognosis.
Fat mass and obesity-associated protein
(
FTO
) functions as an eraser of the RNA m
6
A modification, but its roles in ICC tumorigenesis and development remain unknown. We showed here that the protein level of
FTO
was downregulated in clinical ICC samples and cell lines and that
FTO
expression was inversely correlated with the expression of CA19-9 and micro-vessel density (MVD). A Kaplan-Meier survival analysis showed that a low expression of
FTO
predicted poor prognosis in ICC.
in vitro
, decreased endogenous expression of
FTO
obviously reduced apoptosis of ICC cells. Moreover,
FTO
suppressed the anchorage-independent growth and mobility of ICC cells. Through mining the database,
FTO
was found to regulate the integrin signaling pathway, inflammation signaling pathway, epidermal growth factor receptor (EGFR) signaling pathway, angiogenesis, and the pyrimidine metabolism pathway. RNA decay assay showed that oncogene
TEAD2
mRNA stability was impaired by
FTO
. In addition, the overexpression of
FTO
suppressed tumor growth
in vivo
. In conclusion, our study demonstrated the critical roles of
FTO
in ICC.
...
PMID:Downregulation of Fat Mass and Obesity Associated (FTO) Promotes the Progression of Intrahepatic Cholangiocarcinoma. 3114 5
Fat mass and obesity-associated protein
(
FTO
) has been well known for a pivotal role in regulation of fat mass, adipogenesis and body weight. In recent years, increasing studies revealed a strong association between
FTO
and various types of cancer. Its role in human hepatocellular carcinoma, however, remains unclear. We aimed at investigating the expression pattern and clinical significance of
FTO
in hepatocellular carcinoma. We found that
FTO
mRNA levels were significantly lower in hepatocellular carcinoma tissues. Immunohistochemical analysis showed the expression of
FTO
was reduced in the nuclei in hepatocellular carcinoma, and was associated with AFP level (
P
< 0.001), tumor size (
P
< 0.001), metastasis (
P
= 0.025) and vascular invasion (
P
< 0.001). Patients with decreased
FTO
expression had a shorter overall and tumor-free survival time (
P
= 0.004 and
P
= 0.006) than those with normal
FTO
expression. Cox's proportional hazard regression model revealed that reduced expression of
FTO
was a risk factor associated with the prognosis of
HCC
patients (
P
= 0.022). These results indicated that decreased
FTO
expression is correlated with clinicopathological factors, implying that
FTO
could be a vital predictor of poor outcome in
HCC
patients and serves as a novel biomarker for
HCC
.
...
PMID:Decreased nuclear expression of FTO in human primary hepatocellular carcinoma is associated with poor prognosis. 3193 80
The development of next-generation sequencing technology and the discovery of specific antibodies targeting chemically modified nucleotides have paved the way for a new era of epitranscriptomics. Cellular RNA is known to dynamically and reversibly undergo different chemical modifications after transcription, such as N
6
-methyladenosine (m
6
A), N
1
-methyladenosine, N
6
,2'-O-dimethyladenosine, 5-methylcytosine, and 5-hydroxymethylcytidine, whose identity and location comprise the field of epitranscriptomics. Dynamic post-transcriptional modifications determine the fate of target RNAs by regulating various aspects of their processing, including RNA export, transcript processing, splicing, and degradation. The most abundant internal mRNA modification in eukaryotic cells is m
6
A, which exhibits essential roles in physiological processes, such as embryogenesis, carcinogenesis, and neurogenesis. m
6
A is deposited by the m
6
A methyltransferase complex (composed of METTL3/14/16, WTAP, KIAA1429, and RBM15/15B), erased by demethylases (
FTO
and ALKBH5), and recognised by binding proteins (e.g., YTHDF1/2/3, YTHDC1/2, IGF2BP1/2/3). The liver is the largest digestive and metabolic organ, and m
6
A modifications play unique roles in critical physiological hepatic functions and various liver diseases. This review focuses on the biological roles of m
6
A RNA methylation in lipid metabolism, viral hepatitis, non-alcoholic fatty liver disease,
liver cancer
, and tumour metastasis. In addition, we summarise the existing inhibitors targeting m
6
A regulators and discuss the potential of modulating m
6
A modifications as a therapeutic strategy.
...
PMID:Epitranscriptomics in liver disease: Basic concepts and therapeutic potential. 3233 Jun 3
Liver cancer
is the fourth leading cause of cancer-associated mortality worldwide. Statistics indicate that the incidence of
liver cancer
has been increasing and that its prognosis remains poor.
Fat mass and obesity-associated protein
(
FTO
) is a demethylase that is involved in N6-methyladenosine (m6a) RNA modification; however, to the best of our knowledge, its role in tumorigenesis and development of
liver cancer
remains unknown. In the present study, cell proliferation, colony formation, apoptosis, Transwell and wound healing assays of small interfering (si)RNA-
FTO
HepG2 cells were performed, and the levels of m6A RNA methylation were assessed. Additionally, the prognostic value of
FTO
in
liver cancer
was analyzed using immunohistochemistry analysis. The results from the EpiQuik m6A RNA methylation quantitative assay revealed that knockdown of
FTO
increased the total m6A methylation level. Notably,
FTO
promoted the proliferation and migration of
liver cancer
cells. Additionally,
FTO
expression was upregulated in patients with
liver cancer
and was associated with a high Edmondson Grade, which served as an independent prognostic factor for
liver cancer
. Results from the Kaplan-Meier survival analysis revealed that low expression levels of
FTO
predicted a good prognosis. The 5-year overall survival of the low
FTO
expression group was 68% compared with 48% in the high
FTO
expression group (P=0.077). In conclusion, the present study suggested that
FTO
regulates the tumorigenesis and development of
liver cancer
.
...
PMID:Fat mass and obesity-associated protein promotes the tumorigenesis and development of liver cancer. 3272 83
