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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2024

Open Access 01-12-2024 | Bevacizumab | Research

The synergism of SMC1A cohesin gene silencing and bevacizumab against colorectal cancer

Authors: Maddalena Di Nardo, Simonetta Astigiano, Silvia Baldari, Maria Michela Pallotta, Giovanni Porta, Simona Pigozzi, Annalisa Antonini, Laura Emionite, Annalisa Frattini, Roberto Valli, Gabriele Toietta, Silvia Soddu, Antonio Musio

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2024

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Abstract

Background

SMC1A is a subunit of the cohesin complex that participates in many DNA- and chromosome-related biological processes. Previous studies have established that SMC1A is involved in cancer development and in particular, is overexpressed in chromosomally unstable human colorectal cancer (CRC). This study aimed to investigate whether SMC1A could serve as a therapeutic target for CRC.

Methods

At first, we studied the effects of either SMC1A overexpression or knockdown in vitro. Next, the outcome of SMC1A knocking down (alone or in combination with bevacizumab, a monoclonal antibody against vascular endothelial growth factor) was analyzed in vivo.

Results

We found that SMC1A knockdown affects cell proliferation and reduces the ability to grow in anchorage-independent manner. Next, we demonstrated that the silencing of SMC1A and the combo treatment were effective in increasing overall survival in a xenograft mouse model. Functional analyses indicated that both treatments lead to atypical mitotic figures and gene expression dysregulation. Differentially expressed genes were implicated in several pathways including gene transcription regulation, cellular proliferation, and other transformation-associated processes.

Conclusions

These results indicate that SMC1A silencing, in combination with bevacizumab, can represent a promising therapeutic strategy for human CRC.
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Metadata
Title
The synergism of SMC1A cohesin gene silencing and bevacizumab against colorectal cancer
Authors
Maddalena Di Nardo
Simonetta Astigiano
Silvia Baldari
Maria Michela Pallotta
Giovanni Porta
Simona Pigozzi
Annalisa Antonini
Laura Emionite
Annalisa Frattini
Roberto Valli
Gabriele Toietta
Silvia Soddu
Antonio Musio
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2024
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-024-02976-2

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