@phdthesis{
author = "Marjanović, Jelena",
year = "2019-06-28",
abstract = "Glioblastom, glioma tumor gradusa IV, je najčešći maligni tumor mozga kododraslih i jedan od najsmrtonosnijih tipova tumora. I pored agresivne terapije koja obuhvatahirurško uklanjanje tumora, radio- i hemio-terapiju, prosečno preživljavanje bolesnika saovim tipom tumora je oko 15 meseci. Glioblastom (GBM), pored tumorskih ćelija, sadrži ipopulaciju samo-obnavljajućih tumor-inicirajućih matičnih ćelija (matične ćelijeglioblastoma) koje se smatraju odgovornim za nastanak, progresiju, metastaziranje irezistenciju na terapiju.Geni SOXB1 podgrupe (SOX1, SOX2 i SOX3) kodiraju regulatorne proteine kojiimaju značajne uloge u mnogim procesima u toku razvića, kao što su održavanjepluripotentnosti matičnih ćelija i održavanje populacije neuralnih progenitora upluripotentnom i proliferišućem stanju. Ovi geni imaju i značajne funkcije u procesukarcinogeneze. Ekspresija gena ove podgrupe detektovana je u GBM. Funkcija gena SOX2je dobro proučena kod ovog tipa tumora; pokazano je da ovaj gen promoviše malignipotencijal ćelija GBM i neophodan je za održavanje tumorogenog potencijala matičnihćelija glioblastoma. Za razliku od gena SOX2, uloga gena SOX1 i SOX3 u ćelijama GBMjoš uvek nije dovoljno istražena. Stoga, u okviru ove doktorske disertacije analizirana jeuloga ovih gena u ćelijama glioblastoma.Dobijeni rezultati pokazuju da ćelijske linije GBM eksprimiraju gen SOX1. Poredtoga, u uslovima utišane ekspresije proteina SOX1 detektovano je smanjenjeproliferativnog kapaciteta, vijabilnosti i migratornog potencijala U251 ćelija GBM, kao ipovećanje broja ovih ćelija u senescenciji. Nakon dediferencijacije ćelijskih linija GBMdetektovano je povećanje ekspresije gena SOX1 u poređenju sa ekspresijom uočenom unjihovim parentalnim ćelijama. Nivo ekspresije gena SOX1 povećan je u kulturamamatičnih ćelija glioblastoma u poređenju sa ekspresijom ovog gena u imortalizovanim U87i U251 ćelijama; pri diferencijaciji ovih kultura uočeno je smanjenje ekspresije gena SOX1.Utišavanje ekspresije gena SOX1 u GNS166 kulturi matičnih ćelija GBM dovodi dosmanjenja proliferativnog kapaciteta i vijabilnosti ovih ćelija..., one of deadliest cancers. Despite aggressive treatment, including surgical resection,chemotherapy and radiation, the median survival of patients with glioblastoma is 15months. A growing body of evidence indicates that GBM contains a population of selfrenewingtumor-initiating cells (glioblastoma stem cells - GSCs) that drive tumor initiation,propagation, metastasis and therapy resistance.SOXB1 genes (SOX1, SOX2 and SOX3) encode transcription regulators withimportant roles in embryonic development and carcinogenesis. Literature date revealed thatSOXB1 genes are expressed in GMB tumor samples. The role of one member of this group,SOX2 gene, is well documented in GBM. It was shown that SOX2 gene promotes malignantpotential of GBM cells and it is mandatory for maintenance of tumorogenicity of GSCs.Since the function of SOX1 and SOX3 genes in GBM still remains to be established, theaim of this thesis was to analyze the role of these genes in GBM.Obtained results demonstrated that all analyzed GBM cell lines express SOX1.Downregulation of this gene expression decreases proliferation, viability and migration,and induces senescence of U251 cells. Furthermore, dedifferentiation of GBM cells isaccompanied by increase of SOX1 level compared to that in parental cells. Expression ofthis gene was significantly increased in patient-derived GSC cultures compared to that inU87 and U251 cells; downregulation of SOX1 gene expression was seen upondifferentiation of GSCs. In addition, knock-down of this gene expression reducedproliferation and viability of GSCs.Results obtained in this thesis reveal SOX3 expression in GBM cell lines and tumortissue; the expression of this gene was elevated in the most of analyzed GBM samplescompared to expression levels detected in non-tumoral brain tissues. A high SOX3expression was not associated with the overall survival of GBM patients. Ectopicoverexpression of this gene increased proliferation, viability, migration and invasion ofGBM cells...",
publisher = "Универзитет у Београду, Биолошки факултет",
journal = "Универзитет у Београду",
title = "Analiza uloge gena SOX1 i SOX3 u promovisanju malignog fenotipa ćelija glioblastoma",
url = "https://hdl.handle.net/21.15107/rcub_nardus_11740"
}