The survivin molecule as a double‐edged sword in cellular physiologic and pathologic conditions and its role as a potential biomarker and therapeutic target in cancer

• Published in: Journal of cellular physiology Vol. 235; no. 2; pp. 725 - 744
• Main Authors: Rafatmanesh, Atieh, Behjati, Mohaddeseh, Mobasseri, Narges, Sarvizadeh, Mostafa, Mazoochi, Tahereh, Karimian, Mohammad
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.02.2020
• Subjects: Alleles; Apoptosis; Biomarkers; Cancer; Caspase; Cell division; Cell proliferation; Endothelial cells; Gene expression; Gene therapy; genetic polymorphism; Health risks; Immunotherapy; Leukocytes (neutrophilic); Leukocytes (polymorphonuclear); Lymphocytes; Lymphocytes T; mRNA; Mutation; Polymorphism; Proteins; Survival; Survivin; Therapeutic applications; survivin; gene therapy; cancer; genetic polymorphism; gene expression
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.29027

Survivin is a member of the family of apoptosis inhibitory proteins with increased expression level in most cancerous tissues. Evidence shows that survivin plays regulatory roles in proliferation or survival of normal adult cells, principally vascular endothelial cells, T lymphocytes, primitive hematopoietic cells, and polymorphonuclear neutrophils. Survivin antiapoptotic role is, directly and indirectly, related to caspase proteins and shows its role in cell division through the chromosomal passenger complex. Survivin contains many genetic polymorphisms that the role of some variations has been proven in several cancers. The −31G/C polymorphism is one of the most important survivin mutations which is located in the promoter region on a CDE/CHR motif. This polymorphism can upregulate the survivin messenger RNA. In addition, its allele C can increase the risk of cancers in 1.27‐fold than allele G. Considering the fundamental role of survivin in different cancers, this protein could be considered as a new therapeutic target in cancer treatment. For this purpose, various strategies have been designed including the prevention of survivin expression through inhibition of mRNA translation using antagonistic molecules, inhibition of survivin gene function through small inhibitory molecules, gene therapy, and immunotherapy. In this study, we describe the structure, played roles in physiological and pathological states and genetic polymorphisms of survivin. Finally, the role of survivin as a potential target in cancer therapy given challenges ahead has been discussed. Survivin plays regulatory and pathologic roles in cell function depending on its expression level. Considering the fundamental role of survivin in different cancers, this protein could be considered as a new therapeutic target in cancer treatment.