TY - JOUR
T1 - Competitive Effect of Overexpressed C-terminal of Snail-1 (CSnail) in Control of the Growth and Metastasis of Melanoma Cells
AU - Rostami, Sadegh Paydari
AU - Dehkordi, Negar Moghare
AU - Asgari, Yazdan
AU - Bolouri, Mohammad Reza
AU - Shayanfar, Nasrin
AU - Falak, Reza
AU - Kardar, Gholam Ali
N1 - Publisher Copyright:
© 2024 Bentham Science Publishers.
PY - 2024/1/1
Y1 - 2024/1/1
N2 - 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. Objective: Therefore, interventions on the expression rate of Snails may show beneficial therapeutic applications. 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: 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: 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.
AB - 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. Objective: Therefore, interventions on the expression rate of Snails may show beneficial therapeutic applications. 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: 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: 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.
KW - a tumor suppressor protein p53
KW - Adeno-associated virus
KW - epithelial-mesenchymal transition
KW - melanoma mouse model
KW - metastasis
KW - snail
UR - http://www.scopus.com/inward/record.url?scp=85179306501&partnerID=8YFLogxK
U2 - 10.2174/1574892818666230330105016
DO - 10.2174/1574892818666230330105016
M3 - Article
C2 - 37005514
AN - SCOPUS:85179306501
SN - 1574-8928
VL - 19
SP - 342
EP - 353
JO - Recent Patents on Anti-Cancer Drug Discovery
JF - Recent Patents on Anti-Cancer Drug Discovery
IS - 3
ER -