G-protein Coupled Receptor 34 Promotes Gliomagenesis by Inducing Proliferation and Malignant Phenotype via TGF-Beta/Smad Signaling Pathway.
Technol Cancer Res Treat
; 21: 15330338221105733, 2022.
Article
in En
| MEDLINE
| ID: mdl-35770303
ABSTRACT
Background:
G-protein coupled receptor 34 (GPR34) is involved in cell motility, differentiation, and mitosis. GPR34 was reported to be highly expressed and play an oncogenic role in several solid tumors. Here, we investigated the mechanisms underlying how GPR34 promotes glioma progression.Methods:
Bioinformatic analysis was performed on RNA-seq and clinical data from the gene expression omnibus (GEO), cancer genome atlas (TCGA), and Genotype-Tissue Expression (GTEx) databases. TIMER database and single-sample GSEA (ssGAEA) method were used to investigate the association between the GPR34 expression and immune infiltration level in glioma. Cox regression analysis was employed to ascertain whether the risk signature was an independent prognostic indicator for glioma. The viability and migratory/invasive potential of glioma cells were assessed using Cell Counting Kit-8, colony formation, wound healing, and Transwell assays.Results:
We found that GPR34 expression was positively correlated with immune infiltration level and that high GPR34 level may be associated with poor prognosis in glioma. We further found that GPR34 may serve as an independent prognostic marker and prediction factor for the clinicopathological features of glioma. We showed that knocking down GPR34 attenuated the viability and migratory/invasive capacity of glioma cells (U251 and LN229), while GPR34 overexpression exerted the opposite effects. Additionally, core enrichment in the GSEA analysis indicated that GPR34-mediated gliomagenesis was associated with the cell cycle arrest, epithelial-mesenchymal transition (EMT), and activation of the TGF-ß/Smad pathway; furthermore, inhibiting TGF-ß/Smad signaling using LY2157299, a TGF-ß inhibitor, reversed the oncogenic effects and malignant phenotype associated with GPR34 overexpression.Conclusion:
GPR34 enhances the malignancy and carcinogenesis of glioma by promoting an EMT-like process, G1/S phase cell cycle transition, and TGF-ß/Smad signaling. Accordingly, GPR34 likely functions as an oncogene in glioma and may represent a potential therapeutic target for this cancer.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Epithelial-Mesenchymal Transition
/
Glioma
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Technol Cancer Res Treat
Journal subject:
NEOPLASIAS
/
TERAPEUTICA
Year:
2022
Document type:
Article