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UTJECAJ PROTEINA hMSH3 I INTERLEUKINA-6 NA POJAVNOST MIKROSATELITNE NESTABILNOSTI I DVOLANČANIH LOMOVA DNA U SPORADIČNOM KARCINOMU DEBELOG CRIJEVA
Osjek: Josip Juraj Strossmayer University of Osijek, 2024. urn:nbn:hr:236:468329
Salar, Anamarija
Josip Juraj Strossmayer University of Osijek
Doctoral studies

Institutional repository: Repository of Doctoral School, Josip Juraj University in Osijek

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Salar, A. (2024). UTJECAJ PROTEINA hMSH3 I INTERLEUKINA-6 NA POJAVNOST MIKROSATELITNE NESTABILNOSTI I DVOLANČANIH LOMOVA DNA U SPORADIČNOM KARCINOMU DEBELOG CRIJEVA (Doctoral thesis). Osjek: Josip Juraj Strossmayer University of Osijek. Retrieved from https://urn.nsk.hr/urn:nbn:hr:236:468329

Salar, Anamarija. "UTJECAJ PROTEINA hMSH3 I INTERLEUKINA-6 NA POJAVNOST MIKROSATELITNE NESTABILNOSTI I DVOLANČANIH LOMOVA DNA U SPORADIČNOM KARCINOMU DEBELOG CRIJEVA." Doctoral thesis, Josip Juraj Strossmayer University of Osijek, 2024. https://urn.nsk.hr/urn:nbn:hr:236:468329

Salar, Anamarija. "UTJECAJ PROTEINA hMSH3 I INTERLEUKINA-6 NA POJAVNOST MIKROSATELITNE NESTABILNOSTI I DVOLANČANIH LOMOVA DNA U SPORADIČNOM KARCINOMU DEBELOG CRIJEVA." Doctoral thesis, Josip Juraj Strossmayer University of Osijek, 2024. https://urn.nsk.hr/urn:nbn:hr:236:468329

Salar, A. (2024). 'UTJECAJ PROTEINA hMSH3 I INTERLEUKINA-6 NA POJAVNOST MIKROSATELITNE NESTABILNOSTI I DVOLANČANIH LOMOVA DNA U SPORADIČNOM KARCINOMU DEBELOG CRIJEVA', Doctoral thesis, Josip Juraj Strossmayer University of Osijek, accessed 23 November 2024, https://urn.nsk.hr/urn:nbn:hr:236:468329

Salar A. UTJECAJ PROTEINA hMSH3 I INTERLEUKINA-6 NA POJAVNOST MIKROSATELITNE NESTABILNOSTI I DVOLANČANIH LOMOVA DNA U SPORADIČNOM KARCINOMU DEBELOG CRIJEVA [Doctoral thesis]. Osjek: Josip Juraj Strossmayer University of Osijek; 2024 [cited 2024 November 23] Available at: https://urn.nsk.hr/urn:nbn:hr:236:468329

A. Salar, "UTJECAJ PROTEINA hMSH3 I INTERLEUKINA-6 NA POJAVNOST MIKROSATELITNE NESTABILNOSTI I DVOLANČANIH LOMOVA DNA U SPORADIČNOM KARCINOMU DEBELOG CRIJEVA", Doctoral thesis, Josip Juraj Strossmayer University of Osijek, Osjek, 2024. Available at: https://urn.nsk.hr/urn:nbn:hr:236:468329

Metadata
TitleUTJECAJ PROTEINA hMSH3 I INTERLEUKINA-6 NA POJAVNOST MIKROSATELITNE NESTABILNOSTI I DVOLANČANIH LOMOVA DNA U SPORADIČNOM KARCINOMU DEBELOG CRIJEVA
Title (english)Influence of hMSH3 and interleukin-6 on the occurrence of microsatellite instability and DNA double-stranded breaks in sporadic colon cancer
AuthorAnamarija Salar
MentorTamara Čačev (mentor)
Committee memberMaja Matulić (predsjednik povjerenstva)
GranterJosip Juraj Strossmayer University of Osijek
(Doctoral studies)
Osjek
Defense date and country2024-02-26, Croatia
Scientific / art field,
discipline and subdiscipline		BIOTECHNICAL SCIENCES
Biotechnology
Molecular Biotechnology
Universal decimal classification
(UDC)		577 - Biochemistry. Molecular biology. Biophysics
Abstract
Mikrosatelitna nestabilnost tipa EMAST i MSI rezultat je neispravnog popravka krivo sparenih baza (MMR). EMAST je povezan s premještanjem hMSH3 iz jezgre u citoplazmu gdje ne može sudjelovati u popravku molekule DNA. Potencijalni uzrok ovog premještanja je signalizacija putem IL-6. U ovom radu ispitali smo ekspresiju proteina hMSH3, IL-6 i γH2A.X, kao i status polimorfizama gena MSH3, IL-6, IL-6R i gp130 u oboljelih od sporadičnog karcinoma debelog crijeva obzirom na prisutnost i tip mikrosatelitne nestabilnosti. U našem istraživanju skupine su definirane tako da razlikujemo nestabilnost tipa EMAST koja se javlja samostalno ili udružena s nestabilnosti na dinukleotidnim mikrosatelitnim ponavljanjima (skupina E) odnosno nestabilnost tipa EMAST koja se javlja udruženo s nestabilnost na mononukleotidnim mikrosatelitnim ponavljanjima (skupina M) u odnosu na tumore u kojima nije utvrđena mikrosatelitna nestabilnost (skupina S). U našem istraživanju je u skupinama E i M utvrđen veći udio jezgara negativnih na hMSH3 u odnosu na skupinu S. Nosioci alela C polimorfizma gp130 +148G/C bili su značajno manje zastupljeni u skupini E u odnosu na skupinu S. U tumorima u kojima nisu dokazane mutacije gena TP53 utvrđen je veći udio jezgara pozitivnih na γH2A.X u skupini E u odnosu na skupine S i M. Očekuje se da će rezultati ovog istraživanja doprinijeti razjašnjavanju utjecaja hMSH3 i IL-6 na pojavnost mikrosatelitne nestabilnosti i dvolančanih lomova DNA u sporadičnim karcinomima debelog crijeva.
Abstract (english)
Microsatellite instability, (MSI and EMAST) type, rises from an impaired MMR system. EMAST is associated with the translocation of hMSH3 from the nucleus to the cytoplasm, thereby hindering its role in DNA repair. It has been proposed that IL-6 signaling cascade is implicated in this translocation. In this study, we have investigated the expression of hMSH3, IL-6, and γH2A.X, as well as the status of polymorphisms within the MSH3, IL-6, IL-6R, and gp130 genes in patients with sporadic colorectal cancer in relation to the presence and type of microsatellite instability. In our study, groups were defined to differentiate EMAST instability occurring independently or in association with instability at dinucleotide microsatellite repeats (group E), and EMAST instability occurring combined with instability at mononucleotide microsatellite repeats (group M) compared to tumors where microsatellite instability was not detected (group S). Compared to the group S, groups E and M exhibited a higher percentage of hMSH3 negative nuclei. Carriers of the gp130 +148C allele were less frequent in the group E compared to the group S. In the subset of tumors lacking TP53 mutations, a higher percentage of the γH2A.X positive nuclei was observed in group E compared to the groups S and M. The results of this study might help clarify the role of hMSH3 and IL-6 in the occurrence of microsatellite instability and DNA double-strand breaks in sporadic colon cancer.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:236:468329
Promotion2024
Study programmeTitle: University Postgraduate Interdisciplinary Doctoral Study Molecular Biosciences
Study programme type: university
Study level: postgraduate
Academic / professional title: doktor/doktorica znanosti (doktor/doktorica znanosti)
Type of resourceText
Extent95
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2024-03-21 08:33:44