Oxidative Damage in Sporadic Colorectal Cancer: Molecular Mapping of Base Excision Repair Glycosylases MUTYH and hOGG1 in Colorectal Cancer Patients

0563142 - ÚEM 2023 RIV CH eng J - Článek v odborném periodiku
Kavec, Miriam Julie - Urbanová, M. - Makovický, P. - Opattová, Alena - Tomášová, Kristýna - Kroupa, Michal - Kostovčíková, Klára - Šišková, Anna - Navvabi, Nazila - Schneiderová, M. - Vymetálková, Veronika - Vodičková, Ludmila - Vodička, Pavel
Oxidative Damage in Sporadic Colorectal Cancer: Molecular Mapping of Base Excision Repair Glycosylases MUTYH and hOGG1 in Colorectal Cancer Patients.
International Journal of Molecular Sciences. Roč. 23, č. 10 (2022), č. článku 5704. E-ISSN 1422-0067
Grant CEP: GA ČR(CZ) GA20-03997S; GA MZd(CZ) NU21-03-00506
Institucionální podpora: RVO:68378041 ; RVO:61388971
Klíčová slova: oxidative DNA damage * DNA repair * BER glycosylases * colorectal cancer
Obor OECD: Cell biology
Impakt faktor: 5.6, rok: 2022
Způsob publikování: Open access
https://www.mdpi.com/1422-0067/23/10/5704

Oxidative stress, oxidative DNA damage and resulting mutations play a role in colorectal carcinogenesis. Impaired equilibrium between DNA damage formation, antioxidant status, and DNA repair capacity is responsible for the accumulation of genetic mutations and genomic instability. The lesion-specific DNA glycosylases, e.g., hOGG1 and MUTYH, initiate the repair of oxidative DNA damage. Hereditary syndromes (MUTYH-associated polyposis, NTHL1-associated tumor syndrome) with germline mutations causing a loss-of-function in base excision repair glycosylases, serve as straight forward evidence on the role of oxidative DNA damage and its repair. Altered or inhibited function of above glycosylases result in an accumulation of oxidative DNA damage and contribute to the adenoma-adenocarcinoma transition. Oxidative DNA damage, unless repaired, often gives rise G:C > T:A mutations in tumor suppressor genes and proto-oncogenes with subsequent occurrence of chromosomal copy-neutral loss of heterozygosity. For instance, G>T transversions in position c.34 of a KRAS gene serves as a pre-screening tool for MUTYH-associated polyposis diagnosis. Since sporadic colorectal cancer represents more complex and heterogenous disease, the situation is more complicated. In the present study we focused on the roles of base excision repair glycosylases (hOGG1, MUTYH) in colorectal cancer patients by investigating tumor and adjacent mucosa tissues. Although we found downregulation of both glycosylases and significantly lower expression of hOGG1 in tumor tissues, accompanied with G>T mutations in KRAS gene, oxidative DNA damage and its repair cannot solely explain the onset of sporadic colorectal cancer. In this respect, other factors (especially microenvironment) per se or in combination with oxidative DNA damage warrant further attention. Base excision repair characteristics determined in colorectal cancer tissues and their association with disease prognosis have been discussed as well.
Trvalý link: https://hdl.handle.net/11104/0335181