Opposing Roles of FoxA1 and FoxA3 in Intrahepatic Cholangiocarcinoma Progression.
Bile Duct Neoplasms
/ genetics
Biomarkers, Tumor
/ genetics
Cell Movement
Cell Proliferation
Cholangiocarcinoma
/ genetics
Disease Progression
Female
Follow-Up Studies
Gene Expression Regulation, Neoplastic
Hepatocyte Nuclear Factor 3-alpha
/ genetics
Hepatocyte Nuclear Factor 3-gamma
/ genetics
Humans
Male
Middle Aged
Neoplasm Invasiveness
Prognosis
Survival Rate
Tumor Cells, Cultured
FoxA1
FoxA2
FoxA3
FoxAs
cancer
cholangiocarcinoma
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
05 Mar 2020
05 Mar 2020
Historique:
received:
27
01
2020
revised:
29
02
2020
accepted:
03
03
2020
entrez:
11
3
2020
pubmed:
11
3
2020
medline:
2
12
2020
Statut:
epublish
Résumé
Cholangiocarcinoma (CCA), a malignancy of biliary epithelium, is related to liver stem cell deregulation. FoxAs are a group of transcription factors that play critical roles in liver stem cell differentiation. In this study, the expression levels of FoxAs (i.e., FoxA1, FoxA2 and FoxA3) were detected in intrahepatic CCA tissues and the functions of FoxAs were studied in CCA cell lines. FoxA1 and FoxA2 were mainly localized in the nuclei of normal bile duct (NBD) cells and some of the cancer cells. Low expression of FoxA1 in CCA tissues (72%) was significantly correlated with poor prognosis. FoxA3 expression of CCA cells was localized in the nucleus and cytoplasm, whereas it was slightly detected in NBDs. High expression of FoxA3 in cancer tissues (61%) was significantly related to high metastasis status. These findings suggest the opposing roles of FoxA1 and FoxA3 in CCA. Moreover, the FoxA1-over-expressing CCA cell line exhibited a significant reduction in proliferative and invasive activities compared to control cells. Knockdown of FoxA3 in CCA cells resulted in a significant decrease in proliferative and invasive activities compared with control cells. Taken together, in CCA, FoxA1 is down-regulated and has tumor suppressive roles, whereas FoxA3 is up-regulated and has oncogenic roles.
Identifiants
pubmed: 32151057
pii: ijms21051796
doi: 10.3390/ijms21051796
pmc: PMC7084256
pii:
doi:
Substances chimiques
Biomarkers, Tumor
0
FOXA1 protein, human
0
FOXA3 protein, human
0
Hepatocyte Nuclear Factor 3-alpha
0
Hepatocyte Nuclear Factor 3-gamma
135845-91-9
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Khon Kaen University
ID : 620009001
Organisme : Faculty of Medicine, Khon Kaen University
ID : AS61301
Organisme : Thailand Research Fund
ID : DBG5980004
Déclaration de conflit d'intérêts
The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
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