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Identifikacija in validacija z matičnimi celicami povezanih genov v razvoju in napredovanju raka debelega črevesa in danke : doktorska disertacija
ID Urh, Kristian (Author), ID Boštjančič, Emanuela (Mentor) More about this mentor... This link opens in a new window, ID Zidar, Nina (Co-mentor)

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Abstract
Rak debelega črevesa in danke (RDČD) je med najpogostejšimi rakavimi obolenji. Večina RDČD se pojavi sporadično, poznamo pet stopenj, od zdrave črevesne sluznice, adenomov do napredovalega karcinoma z zasevki. Pomembno vlogo v razvoju RDČD imajo tumorske celice z lastnostmi matičnih celic (MC). Predpostavljamo, da so razlike v izražanju izbranih genov povezane z MC, v razvoju RDČD in da izbrane miRNA regulirajo izbrane gene. Z bioinformatskimi orodji smo analizirali prosto dostopne podatke izražanja RNA, pridobljene s sekvenciranjem in mikromrežami za vzorce adenomov, RDČD in pripadajoče črevesne sluznice. Za nadaljnjo validacijo s kvantitativno verižno reakcijo s polimerazo smo izbrali gene, povezane z MC (ANLN, CDK1, ECT2 L1TD1, PDGFD, SLITRK6, ST6GALNAC1, TCEA3, TNC in TNXB) in napovedane izbrane potencialno regulatorne mikro RNA (miRNA). Za validacijo izražanja smo uporabili tkivne vzorce bolnikov z adenomi, adenomi z zgodnjim RDČD, RDČD brez zasevanja in z zasevanjem. Funkcijo izbranega proteina smo opredelili z utišanjem na celičnih linijah PC3 in HT-29. Pridobili smo dokaze, da je spremenjeno izražanje genov ANLN, ECT2, TCEA3 in TNC potencialno povezano z maligno transformacijo, z zasevanjem pa genov ANLN, CDK1, ECT2, L1TD1, SLITRK6, ST6GALNAC1 in TCEA3. Izbranih genov nismo uspeli povezati z predpostavljenimi potencialno regulatornimi miRNA.

Language:Slovenian
Keywords:rak debelega črevesa in danke, tumorske matične celice, izražanje genov, mikro RNA, bioinformatska analiza
Work type:Doctoral dissertation
Typology:2.08 - Doctoral Dissertation
Organization:BF - Biotechnical Faculty
Year:2023
PID:20.500.12556/RUL-146925 This link opens in a new window
COBISS.SI-ID:155670275 This link opens in a new window
Publication date in RUL:16.06.2023
Views:302
Downloads:59
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Secondary language

Language:English
Title:Identification and validation of stem cell-related genes in colorectal cancerogenesis : doctoral dissertation
Abstract:
Colorectal cancer (CRC) is among the most common cancers. Most CRCs are sporadic, CRC develops in five stages, from healthy mucosa to adenoma and late stage carcinoma. An important role in CRC development could be associated with cancer cells with stem cell properties (SC). We hypothesize that the differences in expression of selected genes are associated with SC in CRC development, and that selected miRNAs regulate these genes. Using bioinformatics tools we analyzed publicly available RNA data obtained with sequencing and microarrays for samples of adenomas, CRC and corresponding colon mucosa. For further validation, using quantitative polymerase chain reaction, we chose genes associated with SC (ANLN, CDK1, ECT2, L1TD1, PDGFD, SLITRK6, ST6GALNAC1, TCEA3, TNC and TNXB) and selected, predicted potentially regulatory microRNAs (miRNAs). For validation of expression we used tissue samples from patients with adenomas, adenomas with early carcinoma, CRC without and with metastases. The function of the selected protein was characterized by silencing in PC3 and HT-29 cell lines. We found evidence that differential expression of genes ANLN, ECT2, TCEA3 and TNC is potentially associated with malignant transformation, while differential expression of genes ANLN, CDK1, ECT2, L1TD1, SLITRK6, ST6GALNAC1 and TCEA3 is potentially associated with metastasizing. We found no significant association between selected potentially regulatory miRNAs and selected genes.

Keywords:colorectal cancer, cancer stem cells, gene expression, microRNA, bioinformatics analysis

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