Investigating the role of PAK3 in drug-induced epithelial-mesenchymal transition and chemoresistance in ovarin cancer cells
2026 (English)Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE credits
Student thesis
Abstract [en]
Ovarian cancer (OC) is the most lethal gynaecological malignancy, with high-grade serous ovarian cancer (HGSOC) accounting for most disease-related deaths. The majority of patients relapse after first-line carboplatin/paclitaxel chemotherapy, and the recurrent disease is typically more invasive and therapy-resistant. Recent studies identified microRNA-103a-3p (miR-103a-3p) as epigenetically silenced in carboplatin-resistant OC cells, with p21-activated kinase 3 (PAK3) as a predicted downstream target showing inverse expression. This thesis aimed to test whether PAK3 functionally drives carboplatin sensitivity, migration, and invasion in OC resistant cells, and to investigate the possible regulatory relationship between miR-103a-3p and PAK3. Paired parental (MES-OV) and carboplatin-resistant (MES-OV CBP) ovarian cancer cells were used throughout. PAK3 silencing by siRNA in MES-OV CBP cells was confirmed by RT-qPCR and Western blot; downstream effects were assessed by Alamar Blue and Boyden chamber assays. miR-103a-3p was inhibited in parental MES-OV cells using a hairpin inhibitor, with miRNA knockdown and PAK3 expression measured from the same cDNA preparation. PAK3 was upregulated in MES-OV CBP cells at both mRNA and protein levels. PAK3 knockdown reduced invasion by 56% and migration by 33%, with the invasion ratio falling from 1.10 to 0.48 after silencing. Carboplatin sensitivity was modestly affected only at low concentrations (10 and 20 μM). miR-103a-3p inhibition produced over 99% knockdown and a 1.5- to 1.65-fold increase in PAK3 mRNA, supporting the predicted inverse regulatory relationship. These data identify PAK3 as a functional driver of invasion in CBP-resistant OC cells, with limited contribution to drug resistance, and provide the first experimental evidence linking miR-103a-3p loss to PAK3 expression in this model.
Place, publisher, year, edition, pages
2026. , p. 24
Keywords [en]
High-grade serous ovarian cancer, carboplatin resistance, EMT, miR-103a-3p, PAK3, invasion, migration, siRNA, Western Blot, MES-OV, MES-OV CBP
National Category
Medical Bioscience
Identifiers
URN: urn:nbn:se:his:diva-26520OAI: oai:DiVA.org:his-26520DiVA, id: diva2:2073403
External cooperation
Ruđer Bošković Institute
Subject / course
Bioscience
Educational program
Molecular Biotechnology - Master’s Programme, 60 ECTS
Supervisors
Examiners
2026-06-162026-06-162026-06-16Bibliographically approved