Cells 2019, 8(2), 128; https://doi.org/10.3390/cells8020128
Regulation of Survivin Isoform Expression by GLI Proteins in Ovarian Cancer
Diana Trnski 1,†, Maja Gregorić 2,†, Sonja Levanat 1, Petar Ozretić 1
, Nikolina Rinčić 1, Tajana Majić Vidaković 1,3, Držislav Kalafatić 4,5, Ivana Maurac 4, Slavko Orešković 4,5, Maja Sabol 1,*
and Vesna Musani 1,*
, Nikolina Rinčić 1, Tajana Majić Vidaković 1,3, Držislav Kalafatić 4,5, Ivana Maurac 4, Slavko Orešković 4,5, Maja Sabol 1,*
and Vesna Musani 1,*
1
Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia
2
Zagreb Health School, Medvedgradska 55, 10000 Zagreb, Croatia
3
PP Orahovica, Pustara 1, 33513 Zdenci, Croatia
4
Department of Obstetrics and Gynaecology, University Hospital Centre Zagreb, Petrova 13, 10000 Zagreb, Croatia
5
School of Medicine, University of Zagreb, Petrova 13, 10000 Zagreb, Croatia
†
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 31 December 2018 / Revised: 1 February 2019 / Accepted: 4 February 2019 / Published: 6 February 2019
(This article belongs to the Special Issue Targeting Hedgehog Signaling in Cancer)
Abstract
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 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. 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. View Full-TextKeywords:
Hedgehog signaling; GLI proteins; survivin; ovarian cancer; isoform expression; polymorphisms
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Trnski, D.; Gregorić, M.; Levanat, S.; Ozretić, P.; Rinčić, N.; Vidaković, T.M.; Kalafatić, D.; Maurac, I.; Orešković, S.; Sabol, M.; Musani, V. Regulation of Survivin Isoform Expression by GLI Proteins in Ovarian Cancer. Cells 2019, 8, 128.
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