E2F1 mediated DDX11 transcriptional activation promotes hepatocellular carcinoma progression through PI3K/AKT/mTOR pathway.
Carcinoma, Hepatocellular
/ genetics
Cell Line, Tumor
Cell Movement
Cell Proliferation
DEAD-box RNA Helicases
/ metabolism
DNA Helicases
/ metabolism
Disease Progression
E2F1 Transcription Factor
/ metabolism
Female
Humans
Liver Neoplasms
/ genetics
Male
Middle Aged
Phosphatidylinositol 3-Kinases
/ metabolism
Proto-Oncogene Proteins c-akt
/ metabolism
Signal Transduction
Transcriptional Activation
/ genetics
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
24 04 2020
24 04 2020
Historique:
received:
19
12
2019
accepted:
09
04
2020
revised:
07
04
2020
entrez:
26
4
2020
pubmed:
26
4
2020
medline:
1
4
2021
Statut:
epublish
Résumé
The DEAD/DEAH box helicase 11 (DDX11) plays vital roles in regulating the initiation of DNA replication. However, its precise function and regulation in hepatocellular carcinoma (HCC) have never been reported yet. In the current study, we found that DDX11 was overexpressed in HCC tissues. High DDX11 expression was positively correlated with large tumor size, tumor multiplicity, late tumor-node-metastasis (TNM) stage and poor prognosis. Additional, gain-of-function and loss-of-function experimental results revealed that DDX11 overexpression promoted HCC cell proliferation, migration, invasion and inhibited cell apoptosis in vitro. Overexpression of DDX11 also enhanced HCC tumorigenicity in vivo. Furthermore, DDX11 was transcriptionally regulated by transcription factor E2F1 in HCC, as demonstrated by chromatin immunoprecipitation (Ch-IP) and luciferase reporter assays. Mechanistically, E2F1/DDX11 axis promoted HCC cell proliferation, migration and invasion, at least in part, through activating PI3K/AKT/mTOR signaling pathway. Conclusively, our study demonstrates that E2F1-enhanced DDX11 expression promotes HCC progression through PI3K/AKT/mTOR pathway and DDX11 might be a potential therapeutic and prognostic target for HCC treatment.
Identifiants
pubmed: 32332880
doi: 10.1038/s41419-020-2478-0
pii: 10.1038/s41419-020-2478-0
pmc: PMC7181644
doi:
Substances chimiques
E2F1 Transcription Factor
0
E2F1 protein, human
0
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
DNA Helicases
EC 3.6.4.-
DDX11 protein, human
EC 3.6.4.13
DEAD-box RNA Helicases
EC 3.6.4.13
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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