Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
Compound
Query: UMLS:C0019204 (
hepatocellular carcinoma
)
71,386
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Ninety percent of all cancer related deaths happen due to metastatic progression. One important protein facilitating metastatic progression in
hepatocellular carcinoma
(
HCC
) is the
metastasis associated 1
protein (MTA-1). We have earlier shown that in the context of
HCC
and normal liver cell lines, HuH6 and THLE-2, respectively. MTA-1 protein is actively stabilized in
HCC
cell lines and actively degraded in normal liver cells. We had also shown that TRIM25 is the E3 ligase that interacts with and degrades MTA-1 protein in normal liver cells. However, the exact mechanism by which TRIM25 degrades MTA-1 protein has still not been elucidated. In the study, we used both in situ prediction algorithms and mass spectrometry based post-translational modification analysis to map the lysine residues in MTA-1 that are polyubiquitinated. Whereas UbPred algorithm revealed a combination of medium and low confidence sites, it revealed only one high confidence lysine (K98) residue. The hCKSAAP_UbSite algorithm also predicted K98 site. Mass spectrometry analysis also showed that K98 has ubiquitin modification. Immunofluorescence analysis showed that in normal liver cell line, THLE-2, which has high expression of TRIM25, ectopically expressed FLAG-tagged wild-type MTA-1 was actively degraded, but the K98R mutant MTA-1 was not. In vitro ubiquitination assay using recombinant wild-type and K98R mutant MTA-1 confirmed that MTA-1 is poly-ubiquitinated at K98 residue by TRIM25. The K98R mutant had a longer half-life than wild-type MTA-1 protein in an in vitro protein stability assay. We establish that TRIM25 ubiquitinates MTA-1 at lysine 98 and degrades it normal liver cells.
...
PMID:Mechanism of TRIM25 mediated ubiquitination of metastasis associated protein (MTA) 1 in normal liver cells. 3011 95
Hepatocellular carcinoma
(
HCC
) is the most common type of liver malignancy with high rates of recurrence and mortality worldwide. Unfortunately, effective strategies for the management of
HCC
are still unsatisfactory. The aim of this investigation is to explore the effects of catalpol on
HCC
progression and investigated the mechanistic functions of catalpol in
HCC
. Catalpol significantly suppressed cell viability, caused the suppression in colony growth, decreased number of invaded and migrated
HCC
cells, and increased the rates of apoptotic cells and proportions of
HCC
cells at G
0
/G
1
cell cycle phase. Furthermore, catalpol dramatically up-regulated miR-22-3p expression in
HCC
cells, and knockdown of miR-22-3p attenuated the anti-tumor effects of catalpol in
HCC
. Additionally, results from luciferase reporter assay demonstrated that miR-22-3p targeted the
metastasis associated 1
family member 3 (MTA3) 3'untranslated region (3'UTR), and miR-22-3p down-regulated MTA3 expression in
HCC
cells. Overexpression of MTA3 enhanced
HCC
cell proliferative abilities, increased the number of invasive and migratory
HCC
cells, and also attenuated the anti-tumor potentials of catalpol in
HCC
. Catalpol suppressed
HCC
tumor growth and increased miR-22-3p expression, while down-regulated MTA3 expression in dissected tumor tissues from xenograft nude mice. Collectively, our results for the first time revealed the anti-tumor potentials of catalpol in
HCC
, and the anti-tumor effects mediated by catalpol were via modulating the miR-22-3p/MTA3 axis in
HCC
.
...
PMID:Catalpol inhibits cell proliferation, invasion and migration through regulating miR-22-3p/MTA3 signalling in hepatocellular carcinoma. 3114 86
The precise molecular mechanism of
hepatocellular carcinoma
(
HCC
) remains ambiguous. Isocitrate dehydrogenase 3A (IDH3A) is known as a subunit of the IDH3 heterotetramer. To the best of our knowledge, the biological effect of IDH3A in malignant tumors is unclear. Here, we report that IDH3A is significantly upregulated in
HCC
tissues; moreover, high expression of IDH3A is strongly associated with tumor size and the clinicopathologic stage of
HCC
. RNA-seq revealed that depletion of IDH3A affects the expression of
metastasis associated 1
(
MTA1
), an oncogene which is related to the progression of numerous cancer types to the metastasis stage. Cell transfection was used to upregulate and downregulate the expression of IDH3A in
HCC
cells. The migration activity of
HCC
cells was assessed using wound healing assays. While transwell assays were carried out to detect the invasion of
HCC
cells. RNA-seq, RT-qPCR and western blot were used to validate
MTA1
as a potential target gene. The present study suggested that IDH3A can upregulate
MTA1
expression and promote epithelial-mesenchymal transition (EMT) in
HCC
by inducing
MTA1
expression, thereby facilitating cell migration and invasion of
HCC
cells. Here, we demonstrated the importance of IDH3A in
HCC
progression. The identification of the IDH3A axis provides novel insight into the pathogenesis of
HCC
, and the IDH3A axis might represent a novel target for the treatment of
HCC
.
...
PMID:Isocitrate dehydrogenase 3A, a rate-limiting enzyme of the TCA cycle, promotes hepatocellular carcinoma migration and invasion through regulation of MTA1, a core component of the NuRD complex. 3316 66
