The role of phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1) in regulating the progression of oral squamous cell carcinoma.
Humans
Adaptor Proteins, Signal Transducing
/ metabolism
Cell Line, Tumor
Cell Movement
Cell Proliferation
/ genetics
Membrane Proteins
/ metabolism
MicroRNAs
/ genetics
Mouth Neoplasms
/ pathology
Phosphatidylinositol 3-Kinases
/ metabolism
Phosphoproteins
/ metabolism
Proto-Oncogene Proteins c-akt
/ metabolism
Squamous Cell Carcinoma of Head and Neck
/ pathology
TOR Serine-Threonine Kinases
/ metabolism
Autophagy
Oral squamous cell carcinoma
Phosphoprotein associated with glycosphingolipid-enriched microdomains 1
Journal
Archives of oral biology
ISSN: 1879-1506
Titre abrégé: Arch Oral Biol
Pays: England
ID NLM: 0116711
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
07
06
2023
revised:
12
09
2023
accepted:
27
09
2023
medline:
6
11
2023
pubmed:
19
10
2023
entrez:
18
10
2023
Statut:
ppublish
Résumé
The aim of this study was to explore the role of the tumor suppressor phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1) on oral squamous cell carcinoma (OSCC) and its molecular mechanism. Immunohistochemistry detected the expression of PAG1 in normal and tumor tissues. The PAG1 overexpressed OSCC cell lines were constructed by lentivirus transfection. Cell Counting Kit-8 assay (CCK-8), clone formation and flow cytometry evaluated the impact of PAG1 on the proliferation and apoptosis of OSCC cells. RNA sequencing (RNA-seq) detected the changes in intracellular genes, and transmission electron microscope (TEM) was used to compare the number of autophagosomes in OSCC cells between Negative and PAG1 group. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and Western blot were used to determine the expression of signaling pathway-related mRNA and proteins respectively. In contrast to the normal tissues, PAG1 expression was significantly downregulated in tumor tissues. Treatment with lentivirus transfection, the expression of PAG1 in the OSCC cell lines was increase. Notably, transfected with PAG1-overexpressing lentivirus cells inhibited the proliferation of OSCC cells and promoted OSCC cells apoptosis. RNA-seq revealed that PAG1 mainly modulated the mitophagy and autophagy pathway, and many autophagosomes were observed in the PAG1 group using TEM. Mechanistically, we found that PAG1 upregulated the expression of autophagy related factors through inhibiting PI3K/Akt/mTOR signal pathway activation. Overexpression of PAG1 inhibited OSCC progression by activating autophagy, its mechanism might be related to inhibition of PI3K/Akt/mTOR signal pathway phosphorylation.
Identifiants
pubmed: 37852106
pii: S0003-9969(23)00198-X
doi: 10.1016/j.archoralbio.2023.105810
pii:
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Membrane Proteins
0
MicroRNAs
0
PAG1 protein, human
0
Phosphatidylinositol 3-Kinases
EC 2.7.1.-
Phosphoproteins
0
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
105810Informations de copyright
Copyright © 2023 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare no competing financial interest.