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MIRnaGLI - Novel Molecular Mechanisms for New Therapeutic Approaches: Interactions of microRNAs and Hedgehog-GLI Signaling Pathway in Serous Ovarian Carcinoma

High-grade serous ovarian cancer is urgent clinical problem (high mortality due to diagnosis at an advanced stage of the disease), and its molecular background is still unknown. Our previous studies showed aberrant activity of the Hedgehog-GLI (Hh-Gli) signaling pathway in ovarian tumors, which is normally active only during embryogenesis and early development, while in adults it may be aberrantly active in tumors. We have shown that aberrant activity of this signaling pathway in ovarian cancer is neither the result of mutations nor of promoter hypermethylation of the main pathway regulators. The next to study are microRNAs (miRNAs), small non-coding double-stranded RNA molecules, which have a key role in post-transcriptional regulation of gene expression. Our preliminary results indicate the connection between the main components of the Hh-Gli and miRNA molecules. We intend to combine the results of miRNA and gene profiling to find miRNAs characteristic for high-grade serous ovarian cancer, implement in vitro and in vivo methods to test functional interaction between miRNAs and their target genes and the influence of altered expression of miRNAs on the phenotype of the tumor cells. The ultimate goal of the project is to find new targets that would contribute to a better prediction, better future therapies as well as understanding the complex molecular interactions. Our hypothesis is that changes in the expression of miRNA molecules related to the Hh-Gli signaling pathway contribute to the development of serous ovarian cancer.

Publications:

Scientific papers:

1. Sabol M, Trnski D, Musani V, Ozretić P, Levanat S. Role of GLI Transcription Factors in Pathogenesis and Their Potential as New Therapeutic Targets. Int J Mol Sci. 2018; 19(9):2562.

2. Trnski D*, Gregorić M*, Levanat S, Ozretić P, Rinčić N, Majić Vidaković T, Kalafatić D, Maurac I, Orešković S, Sabol M, Musani V. Regulation of Survivin Isoform Expression by GLI Proteins in Ovarian Cancer. Cells. 2019; 8(2):128.

Participation in the conferences:

1st Joint EACR-MRS Conference“Seed and Soil In Vivo Models of Metastasis“, Berlin, Germany, 27-29/11/2017

1. Ozretić, Petar; Hackl, Hubert; Trnski, Diana; Sabol, Maja; Kalafatić, Držislav; Musani, Vesna; Levanat, Sonja. Looking for new markers:could microRNA molecules help for earlier diagnosis and better therapies? How (dys)regulation of Hedgehog-Gli signaling pathway contribute to ovarian cancer.

Public discussion „To nisu samo ženske stvari“, Zagreb, Croatia, 08/05/2018

1. Sonja Levanat. Istraživanja mehanizama interakcije steroida i signalnih puteva u razvoju raka jajnika - traženje ranih pokazatelja nastanka raka jajnika

„EACR25: 25th Biennial Congress of the European Association for Cancer Research“, Amsterdam, Netherlands, 30/06-03/07/2018

1. Levanat, Sonja; Ozretić, Petar; Hackl, Hubert; Plattner, Christina; Trnski, Diana; Sabol, Maja; Kalafatić, Držislav; Musani, Vesna. Therapeutic Evaluation Hedgehog-Gli Signaling Pathway through miRNA and mRNA Profiling of Ovarian Carcinoma. ESMO Open 2018;3(Suppl 2):A287-A287.

2. Sabol, Maja; Rinčić, Nikolina; Trnski, Diana; Musani, Vesna; Ozretić, Petar; Levanat, Sonja. Generation of the GLI1, GLI2 and GLI3 knock-out ovarian cancer cell lines using the CRISPR/Cas9. ESMO Open 2018;3(Suppl 2):A300-A300.

„HDIR-5: Translating Science to Medicine - Targets and Therapeutics“ - Fifth Meeting of the Croatian Association for Cancer Research with International Participation, Zagreb, Croatia, 08-10/11/2018

1. Gregorić, Maja; Trnski, Diana; Sabol, Maja; Ozretić, Petar; Levanat, Sonja; Rinčić, Nikolina; Kalafatić, Držislav; Musani, Vesna. Survivin isoform expresion in GLI1-3 knock-out ovarian carcinoma cell lines. Libri Oncologici : Croatian Journal of Oncology, Vol. 46 No. Supplement 1, 2018.

2. Ozretić, Petar; Sabol, Maja; Hackl, Hubert; Plattner, Christina; Trnski, Diana; Kalafatić, Držislav; Musani, Vesna; Zeilinger, Robert; Levanat, Sonja. Interaction of microRNA Molecules and Hedgehog-GLI Signaling Pathway Genes in High-Grade Serous Ovarian Cancer. Libri Oncologici : Croatian Journal of Oncology, Vol. 46 No. Supplement 1, 2018.

3. Rinčić, Nikolina; Sabol, Maja; Trnski, Diana; Musani, Vesna; Ozretić, Petar; Levanat, Sonja. Responsiveness to GANT-61 inhibitor of GLI1, GLI2 and GLI3 knock-out ovarian cancer cell lines. Libri Oncologici : Croatian Journal of Oncology, Vol. 46 No. Supplement 1, 2018.

4. Sabol, Maja. The GLI Code in Ovarian Cancer. Libri Oncologici : Croatian Journal of Oncology, Vol. 46 No. Supplement 1, 2018.

6th SYPOSIUM “APOPTOZA I NOVOTVORINE”, Zagreb, Croatia, 26.03.2019.

1. Trnski, Diana; Gregorić, Maja; Levanat, Sonja; Ozretić, Petar; Rinčić, Nikolina; Majić Vidaković, Tajana; kalafatić, Držislav; Maurac, Ivana; Orešković, Slavko; Sabol, Maja; Musani, Vesna. Utjecaj proteina GLI na regulaciju ekspresije izoformi survivina u karcinomu jajnika.

Diploma thesis:

1. Rinčić, Nikolina. Izrada "knock-out" stanične linije za gen GLI1 primjenom sustava CRISPR/Cas9 / završni rad - diplomski/integralni studij. Zagreb : Prirodoslovno-matematički fakultet, 11/07/2018 Mentor: Sabol, Maja.

Other associates

Vesna Musani, dr.sc.

Senior research associate
Tel:
+385 1 457 1292
Interni broj:
1849

Petar Ozretić, dr.sc.

Research associate
Tel:
+385 1 457 1292
Interni broj:
1849

Maja Sabol, dr.sc.

Research associate
Tel:
+385 1 456 0997
Interni broj:
1753

Diana Trnski, dr.sc.

Postdoctoral researcher
Interni broj:
1849
1512

External Associates:

Doc. dr. sc. Držislav Kalafatić, MD

Dr. sc. Tajana Amšel Zelenika, VMD

Doc. dr. sc. Hubert Hackl

Consultants:

Prof. dr. sc. Robert Zeillinger

Prof. dr. sc. Fritz Aberger

Prof. dr. sc. Regine Schneider-Stock

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