Biomolecules & Therapeutics 2022; 30(4): 380-388  https://doi.org/10.4062/biomolther.2022.063
Snail Promotes Cancer Cell Proliferation via Its Interaction with the BIRC3
Seung Bae Rho1, Hyun-Jung Byun2, Boh-Ram Kim2,* and Chang Hoon Lee2,*
1Division of Cancer Biology, Research Institute, National Cancer Center, Goyang 10408,
2BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University, Seoul/Goyang 04620, Republic of Korea
*E-mail: qtrami@gmail.com (Kim BR), uatheone@dongguk.edu (Lee CH)
Tel: +82-31-961-5434 (Kim BR), +82-31-961-5213 (Lee CH)
Fax: +82-31-961-5206 (Kim BR), +82-31-961-5206 (Lee CH)
Received: May 11, 2022; Revised: May 22, 2022; Accepted: May 28, 2022; Published online: June 17, 2022.
© The Korean Society of Applied Pharmacology. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Snail is implicated in tumour growth and metastasis and is up-regulated in various human tumours. Although the role of Snails in epithelial-mesenchymal transition, which is particularly important in cancer metastasis, is well known, how they regulate tumour growth is poorly described. In this study, the possible molecular mechanisms of Snail in tumour growth were explored. Baculoviral inhibitor of apoptosis protein (IAP) repeat-containing protein 3 (BIRC3), a co-activator of cell proliferation during tumourigenesis, was identified as a Snail-binding protein via a yeast two-hybrid system. Since BIRC3 is important for cell survival, the effect of BIRC3 binding partner Snail on cell survival was investigated in ovarian cancer cell lines. Results revealed that Bax expression was activated, while the expression levels of anti-apoptotic proteins were markedly decreased by small interfering RNA (siRNA) specific for Snail (siSnail). siSnail, the binding partner of siBIRC3, activated the tumour suppressor function of p53 by promoting p53 protein stability. Conversely, BIRC3 could interact with Snail, for this reason, the possibility of BIRC3 involvement in EMT was investigated. BIRC3 overexpression resulted in a decreased expression of the epithelial marker and an increased expression of the mesenchymal markers. siSnail or siBIRC3 reduced the mRNA levels of matrix metalloproteinase (MMP)-2 and MMP-9. These results provide evidence that Snail promotes cell proliferation by interacting with BIRC3 and that BIRC3 might be involved in EMT via binding to Snail in ovarian cancer cells. Therefore, our results suggested the novel relevance of BIRC3, the binding partner of Snail, in ovarian cancer development.
Keywords: Snail, BIRC3, Yeast two-hybrid, P53, Proliferation, Ovarian cancer


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