3rd International Conference on Chemo and BioInformatics, Kragujevac, September 25-26. 2025. (pp. 292-295)
АУТОР(И) / AUTHOR(S): Zorana Dobrijević, Sanja Goč, Jovana Vuković, Andrea Pirković
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DOI: 10.46793/ICCBIKG25.292D
САЖЕТАК / ABSTRACT:
Our recent study demonstrated the ameliorative effect of extracellular vesicles (EVs) from trophoblast cells (TC-EVs) on ovarian cancer (OC) A2780 cells’ sensitivity to cisplatin, likely via modulation of pro-apoptotic pathways. However, the mechanisms and the exact constituents of EVs which display pro-apoptotic effect in recipient cells remain unclear. The aim of this study is to investigate via in silico analysis whether microRNAs present in TC-EVs produced by HTR- 8/SVneo cells could mediate the observed pro-apoptotic effect in OC and exert other cancer phenotype-related mechanisms. MicroRNA profiling results of TC-EVs were extracted from GEO dataset GSE182717 and microRNAs were ranked according to normalized read counts. Among 75 microRNAs presented with average rpm≥1000, 30 were identified as BCL2 regulators. After the exclusion of microRNAs highly expressed in recipient A2780 cells, microRNA-mRNA network topology analysis identified 11 hub TC-EVs-abundant microRNAs. Gene ontology (GO) analyses indicated that potential targets of these hub microRNA genes were concentrated predominantly on “MAPKKK activity”, “regulation of DNA-dependent transcription, elongation” and “ligase activity, forming carbon-oxygen” (molecular function category), while most hits belonged to “Pathways in cancer” and “MAPK signaling pathway”. Prioritizing of potential candidates for future experimental validation relied on identifying hits for the most abundant TC-EVs BCL2– targeting microRNAs within a panel of downregulated microRNAs from cisplatin resistant OC cell lines (GSE1617848) and literature-supported effects on BCL2 expression in OC. The most plausible candidate for TC-EVs-A2780 delivery analysis was found to be miR-16-5p. The presented results illustrate the potential relation between the delivery of TC-EVs microRNAs and apoptotic pathway activation in A2780. Additional findings on TC-EVs microRNA functions and candidate microRNA delivery are required for further interpretation of the contributing effect of microRNAs on experimentally observed changes in TC-EVs-treated A2780 cells.
КЉУЧНЕ РЕЧИ / KEYWORDS:
ovarian cancer, trophoblast, microRNA, extracellular vesicles.
ПРОЈЕКАТ / ACKNOWLEDGEMENT:
This research is funded by the Ministry of Science, Technological Development and Innovation, Republic of Serbia, Contract No: 451-03-136/2025-03/200019.
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