Uloga izoformi ciklooksigenaza u tumorigenezi sporadičnoga karcinoma debeloga crijeva

doctoral thesis

• Title (english): The role of cyclooxygenase isoforms in sporadic colorectal carcinogenesis
• Author: Tina Catela Ivković
• Mentor: Sanja Kapitanović (mentor)
• Committee member: Nada Oršolić (član povjerenstva)
• Committee member: Marijana Popović Hadžija (član povjerenstva)
• Committee member: Maja Sirotković-Skerlev (član povjerenstva); MBZ: 119524
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2014, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Universal decimal classification (UDC): 577 - Biochemistry. Molecular biology. Biophysics

Abstract

Ciklooksigenaze su ključni enzimi u biosintezi prostanoida. Postoje dvije izoforme: COX-1 koja je povezana s održavanjem fizioloških uvjeta u sluznici debelog crijeva; te inducibilna izoforma COX-2 koja je uglavnom povezana s patološkim procesima uključujući karcinom debelog crijeva. Cilj ovog istraživanja bio je ispitati ulogu COX izoformi u razvoju i napredovanju sporadičnoga karcinoma debeloga crijeva, mehanizme njihove regulacije te povezanost regulatornih polimorfizama gena COX-1 i COX-2 sa sklonošću obolijevanju i ekspresijom mRNA i proteina. Naši rezultati su pokazali da COX-1 ima zaštitnu, a COX-2 tumorigenu ulogu u sluznici debelog crijeva. Gubitak COX-1 učestali je događaj u karcinogenezi, dok COX-2 pokazuje veću varijaciju između uzoraka. Porast COX-2 ekspresije povezan je s lošijim preživljenjem oboljelih. Dokazali smo povezanost regulatornih polimorfizama sa sklonošću obolijevanju i ekspresijom gena COX-2. Ekspresija proteina odgovara mRNA ekspresiji te nema povezanosti s ekspresijom miR-200 što pokazuje da je ekspresija gena COX-1 i COX-2 primarno regulirana na razini transkripcije.

Abstract (english)

Cyclooxygenases are the key enzymes in prostanoid biosynthesis. Two isoforms exist: COX-1, associated with maintainance of physiological conditions in colon; and inducible COX-2 that is mainly related to various pathologies including colorectal cancer. The aim of our study was to examine the role of COX isoforms in development and progression of sporadic colorectal cancer, mechanisms of their regulation and whether regulatory polymorphisms in COX genes are related to cancer susceptibility, mRNA and protein expression. Our results show that COX-1 has protective, and COX-2 tumorigenic role in colorectal mucosa. Loss of COX-1 is very frequent in carcinogenesis, while COX-2 shows greater variation between samples. Higher COX-2 expression correlates to worse patient survival. We proved the role of regulatory polymorphisms in cancer susceptibility, and COX-2 expression. Protein expression correlates with mRNA expression, and there is no associtation with miR-200, which indicates transcriptional regulation as the key regulatory mechanism of COX expression.

• Keywords: COX-1; COX-2; karcinom debelog crijeva; polimorfizmi; ekspresija; miR-200
• Keywords (english): COX-1; COX-2; sporadic colorectal cancer; SNP; expression; miR-200
• Language: croatian
• URN:NBN: urn:nbn:hr:217:610301
• Study programme: Title: Biology; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija (doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-05-17 12:39:30