Competitive Effect of Overexpressed C-terminal of Snail-1 (CSnail) in Control of the Growth and Metastasis of Melanoma Cells.
Adeno-associated virus
Epithelial-mesenchymal transition
Melanoma mouse model
Metastasis
Snail
a Tumor suppressor protein p53
Journal
Recent patents on anti-cancer drug discovery
ISSN: 2212-3970
Titre abrégé: Recent Pat Anticancer Drug Discov
Pays: United Arab Emirates
ID NLM: 101266081
Informations de publication
Date de publication:
30 Mar 2023
30 Mar 2023
Historique:
received:
12
12
2022
revised:
09
02
2023
accepted:
21
02
2023
entrez:
3
4
2023
pubmed:
4
4
2023
medline:
4
4
2023
Statut:
aheadofprint
Résumé
Epithelial-to-mesenchymal transition (EMT) plays a role in the invasion and metastasis of cancer cells. During this phenomenon, Snail can promote tumor progression by upregulating mesenchymal factors and downregulating the expression of pro-apoptotic proteins. Therefore, interventions on the expression rate of Snails may show beneficial therapeutic applications. In this study, the C-terminal region of Snail1, capable of binding to E-box genomic sequences, was subcloned into the pAAV-IRES-EGFP backbone to make complete AAV-CSnail viral particles. B16F10 as a metastatic melanoma cell line, with a null expression of wild type TP53 was transduced by AAV-CSnail. Moreover, the transduced cells were analyzed for in-vitro expression of apoptosis, migration, and EMT-related genes, and in-vivo inhibition of metastasis. In more than 80% of the AAV-CSnail transduced cells, the CSnail gene expression competitively reduced the wild-type Snail functionality and consequently lowered the mRNA expression level of EMT-related genes. Furthermore, the transcription level of cell cycle inhibitory factor p21 and pro-apoptotic factors were promoted. The scratch test showed a decrease in the migration ability of AAV-CSnail transduced group compared to control. Finally, metastasis of cancer cells to lung tissue in the AAV-CSnail-treated B16F10 melanoma mouse model was significantly reduced, pointing out to prevention of EMT by the competitive inhibitory effect of CSnail on Snail1 and increased apoptosis of B16F10 cells. The capability of this successful competition in reducing the growth, invasion, and metastasis of melanoma cells indicates that gene therapy is a promising strategy for the control of the growth and metastasis of cancer cells.
Sections du résumé
BACKGROUND
BACKGROUND
Epithelial-to-mesenchymal transition (EMT) plays a role in the invasion and metastasis of cancer cells. During this phenomenon, Snail can promote tumor progression by upregulating mesenchymal factors and downregulating the expression of pro-apoptotic proteins.
OBJECTIVES
OBJECTIVE
Therefore, interventions on the expression rate of Snails may show beneficial therapeutic applications.
METHODS
METHODS
In this study, the C-terminal region of Snail1, capable of binding to E-box genomic sequences, was subcloned into the pAAV-IRES-EGFP backbone to make complete AAV-CSnail viral particles. B16F10 as a metastatic melanoma cell line, with a null expression of wild type TP53 was transduced by AAV-CSnail. Moreover, the transduced cells were analyzed for in-vitro expression of apoptosis, migration, and EMT-related genes, and in-vivo inhibition of metastasis.
RESULTS
RESULTS
In more than 80% of the AAV-CSnail transduced cells, the CSnail gene expression competitively reduced the wild-type Snail functionality and consequently lowered the mRNA expression level of EMT-related genes. Furthermore, the transcription level of cell cycle inhibitory factor p21 and pro-apoptotic factors were promoted. The scratch test showed a decrease in the migration ability of AAV-CSnail transduced group compared to control. Finally, metastasis of cancer cells to lung tissue in the AAV-CSnail-treated B16F10 melanoma mouse model was significantly reduced, pointing out to prevention of EMT by the competitive inhibitory effect of CSnail on Snail1 and increased apoptosis of B16F10 cells.
CONCLUSION
CONCLUSIONS
The capability of this successful competition in reducing the growth, invasion, and metastasis of melanoma cells indicates that gene therapy is a promising strategy for the control of the growth and metastasis of cancer cells.
Identifiants
pubmed: 37005514
pii: PRA-EPUB-130519
doi: 10.2174/1574892818666230330105016
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
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