Uloga polimorfizma gena TLR5 u nastanku karcinoma pluća

doctoral thesis

• Title (english): The role of TLR5 polymorphism in lung cancer development
• Author: Gordana Drpa
• Mentor: Jelena Knežević (mentor)
• Mentor: Suzana Kukulj (komentor)
• Committee member: Nada Oršolić (predsjednik povjerenstva)
• Committee member: Inga Urlić (član povjerenstva)
• Committee member: Miroslav Samaržija (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2022-05-23, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Universal decimal classification (UDC): 577 - Biochemistry. Molecular biology. Biophysics

Abstract

Otkriće receptora TLR dovelo je do novih spoznaja o imunosnim procesima u stanicama.
Ovim receptorima, kao i polimorfizmima njihovih gena, pripisuje se vaţna uloga u
nastanku mnoštva bolesti, ukljuĉujući karcinome. Prema dostupnoj literaturi, u ovom je
radu prvi put ispitivana uloga polimorfizma rs2072493/N592S u genu TLR5 kod karcinoma
pluća. Ciljevi rada bili su funkcionalna procjena varijante i identifikacija proliferacijskog
kapaciteta stanica s varijantom. U radu su korištene staniĉne linije zdravih pluća i
karcinoma pluća u koje su uneseni plazmidi ili adenovirusni konstrukti s divljim tipom ili
varijantom N592S. Tako dobivene stanice stimulirane su flagelinom. U stanicama je potom
izmjerena sposobnost prijenosa signala i razina ekspresije specifiĉnih proteina, a ispitan je i
utjecaj varijante na staniĉnu pokretljivost i vijabilnost. UtvrĊeno je da je varijanta N592S
funkcionalna te da je porast aktivnosti NF-κB nakon stimulacije flagelinom u stanicama s
varijantom slabiji. Na proteinskoj razini naĊene su razlike u aktivnosti nizvodnih signalnih
molekula u ovisnosti o prisustvu varijante kao i znaĉajno manja pokretljivost i vijabilnost
stanica s prekomjernom ekspresijom varijante u odnosu na divlji tip gena TLR5.

Abstract (english)

The discovery of Toll-like receptors led to new insights into cellular immune processes.
These receptors, as well as their genetic polymorphisms, are attributed an important role in
the development of many diseases, including cancer. Based on the available literature, this
is the first research into the role of the rs2072493/N592S polymorphism in the TLR5 gene
in lung cancer. The objectives of this work were a functional evaluation of the variant as
well as the identification of the proliferative capacity of cells carrying the variant. Healthy
lung and lung cancer cell lines with inserted plasmids or adenovirus constructs containing
wild-type or the rs2072493/N592S variant were used in the research. Following the
stimulation of the thus obtained cells with flagellin, the ability of signal transmission,
specific protein expression, as well as cell viability and migration were measured in the
cells. The N592S variant was found to be functional, and it was established that after
stimulation with flagellin, the increase in NF-κB activity in cells with the variant was
lower. On the protein level, differences in the activity of downstream signaling molecules
depending on the presence of the variant were observed, as well as a significantly lower
mobility and viability of cells with the variant in comparison to wild-type TLR5 gene.

• Keywords: karcinom pluća; priroĊena imunost; polimorfizam gena; Tollu sliĉni receptori; rs2072493/N592S varijanta
• Keywords (english): lung cancer; innate immunity; gene polymorphism; toll-like receptors; rs2072493/N592S variant
• Language: croatian
• URN:NBN: urn:nbn:hr:217:458198
• Promotion: 2022
• 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: 2022-11-21 11:40:31