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

Preview

PDF - Published Version - article Available under License Creative Commons Attribution. Download (1MB) | Preview

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 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
Projects:	Project title Project leader Project code Project type Novi molekularni mehanizmi kao mete ciljanih terapija: Interakcije molekula mikroRNA i signalnog puta Hedgehog-GLI u seroznom karcinomu jajnika-MIRnaGLI Sonja Levanat IP-2016-06-1268 HRZZ The Terry Fox Foundation UNSPECIFIED UNSPECIFIED UNSPECIFIED
Depositing User:	Maja Sabol
Date Deposited:	09 Apr 2019 13:52
URI:	http://fulir.irb.hr/id/eprint/4474
DOI:	10.3390/cells8020128

Actions (login required)

View Item