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)
Hepatocellular carcinoma
(
HCC
) prognosis remains dismal due to postsurgical recurrence and distant metastasis. Therefore, novel prognostic biomarkers and therapeutic targets for
HCC
therapy are urgently needed to improve the survival of liver cancer patients. Our evidence suggests that
SLC46A3
(the gene solute carrier family 46 (sodium phosphate), member 3) is a member of the SLC46 family and has a potential role in the progression and treatment of
HCC
. The objective of the present study was to estimate the expression pattern and biological function of
SLC46A3
in the progression of
HCC
, which may serve as a promising biomarker for diagnosis and therapy. In order to determine the expression pattern of
SLC46A3
in
HCC
, several public
HCC
databases and tissue chips were used to examine 129 sets of primary
HCC
and non-tumor adjacent tissues from patients who had undergone surgery. The expression of
SLC46A3
in 80 sets of
HCC
and non-tumor adjacent tissues were then compared by RT-PCR and Western Blot. The proliferation, invasion, migration and sphere-forming abilities of
SLC46A3
knock-down and overexpressing cell lines were evaluated and the expression of related molecules in the epithelial mesenchymal transition (EMT) were detected by RT-PCR, western blot and immunofluorescence assay. The IC
50
value was used to evaluate the effect of
SLC46A3
on sorafenib resistance. A lung metastasis model of mice
HCC
was constructed to test the potential effect of
SLC46A3
on cancer metastasis and a subcutaneous xenografted tumor mice model was designed to verify the effect of
SLC46A3
on the resistance of
HCC
cell lines to sorafenib. The expression of
SLC46A3
was down-regulated in 83.2% of human
HCC
tissues compared to non-tumor adjacent tissues. Tumors that expressed low levels of
SLC46A3
had more aggressive phenotypes, and patients with these tumors had shorter survival times after surgery compared to patients whose tumors expressed high levels of
SLC46A3
.
Hepatocellular carcinoma
cell lines that stably overexpressed
SLC46A3
inhibited the levels of migration and invasion compared with control
HCC
cells, and formed smaller xenograft tumors with more metastases in mice compared with
HCC
cells that did not overexpress
SLC46A3
. In addition, overexpression of
SLC46A3
obviously inhibited epithelial-to-mesenchymal transition-activating transcription factors such as N-cadherin and Vimentin. Furthermore, descended of IC
50
showed that overexpressed
SLC46A3
could reduce sorafenib resistance and improve drug response in vivo and in vitro. In conclusion, increased expression of
SLC46A3
could favor a better clinical prognosis for patients with
HCC
, ameliorate sorafenib resistance, and improve drug response.
SLC46A3
might serve as a potential prognostic biomarker and therapeutic target in
HCC
.
...
PMID:Increased expression of SLC46A3 to oppose the progression of hepatocellular carcinoma and its effect on sorafenib therapy. 3098 Nov 7
