Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Snail Promotes Cancer Cell Proliferation via Its Interaction with the BIRC3

  • Rho, Seung Bae (Division of Cancer Biology, Research Institute, National Cancer Center) ;
  • Byun, Hyun-Jung (BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University) ;
  • Kim, Boh-Ram (BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University) ;
  • Lee, Chang Hoon (BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University)
  • Received : 2022.05.11
  • Accepted : 2022.05.28
  • Published : 2022.07.01
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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

Acknowledgement

This work was supported by grants from the National Cancer Center (NCC-2112500-1) and the Basic Science Research Program NRF (NRF-2020R1A2C3004973), NRF (NRF-2018R1A5A2023127), and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Korea (HP20C0131).

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