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Regulation of Survivin Isoform Expression by GLI Proteins in Ovarian Cancer

Trnski, Diana; Gregorić, Maja; Levanat, Sonja; Ozretić, Petar; Rinčić, Nikolina; Majić Vidaković, Tajana; kalafatić, Držislav; Maurac, Ivana; Orešković, Slavko; Sabol, Maja; Musani, Vesna (2019) Regulation of Survivin Isoform Expression by GLI Proteins in Ovarian Cancer. Cells, 8 (2). ISSN 2073-4409

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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 pathway is the 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 GLI proteins in the regulation of survivin isoform expression (WT, 2α, 2B, 3B and Δex3) 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. Combined tTreatment of GLI1 knock-out cells line with GANT-61 shows an additional inhibitory effect of GANT-61 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.

Item Type: Article
Uncontrolled Keywords: Hedgehog signaling ; GLI proteins ; ovarian cancer ; isoform expression: polymorphisms
Subjects: BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences
Divisions: Division of Molecular Medicine
Project titleProject leaderProject codeProject type
Novi molekularni mehanizmi kao mete ciljanih terapija: Interakcije molekula mikroRNA i signalnog puta Hedgehog-GLI u seroznom karcinomu jajnika-MIRnaGLISonja LevanatIP-2016-06-1268HRZZ
Depositing User: Maja Sabol
Date Deposited: 09 Apr 2019 13:52
DOI: 10.3390/cells8020128

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