HBXIP Regulates Gastric Cancer Glucose Metabolism and Malignancy Through PI3K/AKT and p53 Signaling.
HBXIP
PI3K/AKT
gastric cancer
glucose metabolism
p53
Journal
OncoTargets and therapy
ISSN: 1178-6930
Titre abrégé: Onco Targets Ther
Pays: New Zealand
ID NLM: 101514322
Informations de publication
Date de publication:
2020
2020
Historique:
received:
21
12
2019
accepted:
30
03
2020
entrez:
6
5
2020
pubmed:
6
5
2020
medline:
6
5
2020
Statut:
epublish
Résumé
Hepatitis B X-interacting protein (HBXIP) overexpression is related to the progression of multiple cancers. However, its role in gastric cancer (GC) remains unclear. HBXIP expression was determined in human GC specimens and cell lines by quantitative polymerase chain reaction (qRT-PCR) and Western blot. The effects of HBXIP depletion or ectopic expression on GC proliferation were evaluated in vitro using the cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) incorporation, colony formation, and cell cycle assays. The in vivo effects were investigated using a mouse xenograft model. Apoptosis was evaluated by flow cytometry (in vitro) and immunohistochemistry (IHC; in vivo). Cell migration and invasion were evaluated in vitro using wound healing, transwell migration, and matrigel invasion assays; and in vivo by quantifying distant metastases from injection of GC cells in the lateral tail vein. Herein, we reported that HBXIP expression was higher in GC than in normal tissues, and this high expression indicated a poorer prognosis. Gain- and loss-of-function assays showed that HBXIP promoted GC proliferation, migration, and invasion, and inhibited apoptosis. High-performance liquid chromatography (HPLC) quantification of glycolytic metabolites revealed that HBXIP promoted glucose metabolic reprogramming. Investigation of the PI3K/AKT and p53 pathways highlighted their role in this HBXIP-mediated metabolic reprogramming. Our results indicate that the up-regulation of HBXIP leads to GC progression by positively regulating glucose metabolism. Therefore, HBXIP is a potential target for the treatment of GC.
Identifiants
pubmed: 32368094
doi: 10.2147/OTT.S243250
pii: 243250
pmc: PMC7183336
doi:
Types de publication
Journal Article
Langues
eng
Pagination
3359-3374Informations de copyright
© 2020 Qiu et al.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest in this work.
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