Regulation of survivin isoform expression by GLI proteins in ovarian cancer

Scientific paper - Original scientific paper

• Author: Diana Trnski
• Author: Maja Gregorić
• Author: Sonja Levanat
• Author: Petar Ozretić
• Author: Nikolina Rinčić
• Author: Tajana Vidaković
• Author: Držislav Kalafatić
• Author: Ivana Maurac
• Author: Slavko Orešković
• Author: Maja Sabol
• Author: Vesna Musani
• Author's institution: University of Zagreb; School of Medicine
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences

Abstract (english)

Ovarian cancer (OC) is the most lethal female gynecological malignancy, mostly due to
diagnosis in late stages when treatment options are limited. Hedgehog-GLI (HH-GLI) signaling
is a major developmental pathway involved in organogenesis and stem cell maintenance, and is
activated in OC. One of its targets is survivin (BIRC5), an inhibitor of apoptosis protein (IAP) that
plays a role in multiple processes, including proliferation and cell survival. We wanted to investigate
the role of different... More GLI proteins in the regulation of survivin isoform expression (WT, 2α, 2B, 3B,
and Dex3) in the SKOV-3 OC cell line. We demonstrated that survivin isoforms are downregulated in
GLI1 and GLI2 knock-out cell lines, but not in the GLI3 knock-out. Treatment of GLI1 knock-out cells
with GANT-61 shows an additional inhibitory effect on several isoforms. Additionally, we examined
the expression of survivin isoforms in OC samples and the potential role of BIRC5 polymorphisms
in isoform expression. Clinical samples showed the same pattern of survivin isoform expression as
in the cell line, and several BIRC5 polymorphisms showed the correlation with isoform expression.
Our results showed that survivin isoforms are regulated both by different GLI proteins and BIRC5
polymorphisms in OC. Less

• Keywords (english): Alternative Splicing / genetics; Case-Control Studies; Cell Line, Tumor; Exons / genetics; Female; Humans; Linkage Disequilibrium / genetics; Ovarian Neoplasms / genetics; Ovarian Neoplasms / metabolism; Protein Isoforms / genetics; Protein Isoforms / metabolism; Pyridines / pharmacology; Pyrimidines / pharmacology; Survivin / genetics; Survivin / metabolism; Trans-Activators / metabolism
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Published version
• Journal title: Cells
• Numbering: vol. 8, no. 2, p. 128
• p-ISSN: 2073-4409
• DOI: https://doi.org/10.3390/cells8020128
• URN:NBN: urn:nbn:hr:105:649012
• Publication: 2019-02-06
• Document URL: http://doi.org/10.3390/cells8020128
• Type of resource: Text
• Access conditions: Open access
• Created on: 2024-03-28 10:28:05