Uloga molekula mikroRNA miR-16-5p i miR-107 u regulaciji ekspresije gena BRCA1 i BRCA2 u seroznom raku jajnika visokog stupnja malignosti

master's thesis

• Title (english): The role of miR-16-5p and miR-107 microRNAs in the regulation of BRCA1 and BRCA2 gene expression in high-grade serous ovarian cancer
• Author: Petra Perić
• Mentor: Petar Ozretić (mentor)
• Mentor: Nada Oršolić (komentor)
• Committee member: Nada Oršolić (predsjednik povjerenstva)
• Committee member: Jasna Lajtner (član povjerenstva)
• Committee member: Petar Kružić (član povjerenstva)
• Committee member: Maja Matulić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2023-02-28, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Serozni rak jajnika visokog stupnja malignosti (HGSOC) najčešći je i najsmrtonosniji podtip
raka jajnika. Često je otkriven u uznapredovanoj fazi zbog izostanka jasnih i ranih simptoma,
ali i nedostatka pouzdanih testova za rano otkrivanje. Glavni cilj ovog diplomskog rada je na
proširenom setu uzoraka tkiva HGSOC i zdravih jajovoda odrediti ekspresiju mikroRNA hsamiR-16-5p i hsa-miR-107 te gena BRCA1 i BRCA2, za koje je utvrđeno da su njihovi ciljni
geni, a čija bi poremećena ekspresija mogla biti uzrokovana poremećenom ekspresijom ovih
mikroRNA. Određena je i dijagnostička vrijednost dobivenih ekspresija u razlikovanju
tumorskog od zdravog tkiva. Osim toga, na staničnoj liniji karcinoma jajnika OVCAR-8
istražen je utjecaj tretmana mimicima i inhibitorima miR-16-5p i miR-107 na ekspresiju gena
BRCA1 i BRCA2. Rezultati su pokazali da je ekspresija gena BRCA2 i obje miRNA značajno
povećana u raku jajnika, te da postoji pozitivna korelacija između ekspresija istraživanih gena,
ali i miRNA, te miR-107 i BRCA2. Ovakav rezultat ujedno ukazuje na moguću povezanost u
regulaciji njihove ekspresije. Najveću dijagnostičku vrijednost pokazale su ekspresije BRCA2 i
miR-107 (AUC > 0,8). Općenito, tretmani mimicima i inhibitorima su pokazali pozitivan
utjecaj na ekspresiju oba gena, pri čemu je tretman inhibitorom miR-107 pokazao jednak utjecaj
kao i mimik.

Abstract (english)

High-grade serous ovarian cancer (HGSOC) is the most common and deadliest subtype of
ovarian cancer. It is often detected at an advanced stage due to the absence of clear and early
symptoms, but also the lack of reliable tests for early detection. The main objective of this thesis
was to determine the expression of microRNAs hsa-miR-16-5p and hsa-miR-107 and BRCA1/2
genes, which were found to be their target genes, on an expanded set of HGSOC tissue samples
and healthy fallopian tubes, and whose impaired expression could be caused by impaired
expression of these microRNAs. The diagnostic value of the obtained expressions in
distinguishing tumor from healthy tissue was also determined. In addition, the influence of
treatment with miR-16-5p and miR-107 mimics and inhibitors on the expression of BRCA1 and
BRCA2 genes was investigated on the OVCAR-8 ovarian cancer cell line. The results showed
that the expression of the BRCA2 gene and both miRNAs was significantly increased in ovarian
cancer, and that there was a positive correlation between expression of investigated genes, but
also miRNAs, and miR-107 and BRCA2. This result also indicates potential connection in the
regulation of their expression. The highest diagnostic values were shown for the expressions of
BRCA2 and miR-107 (AUC > 0.8). Generally, treatments with mimics and inhibitors showed a
positive effect on the expression of both genes, but inhibitor miR-107 treatment showed the
same effect as the mimic.

• Keywords: HGSOC; mikroRNA; BRCA1; BRCA2; ekspresija; qRT-PCR
• Keywords (english): HGSOC; microRNA; BRCA1; BRCA2; expression; qRT-PCR
• Language: croatian
• URN:NBN: urn:nbn:hr:217:384115
• Study programme: Title: Experimental Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra eksperimentalne biologije (magistar/magistra eksperimentalne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2025-02-28
• Created on: 2023-03-13 09:52:11