8-Oxoguanine DNA Glycosylase 1 Upregulation as a Risk Factor for Obesity and Colorectal Cancer

Jesús Pilo; Libia Alejandra García-Flores; Mercedes Clemente-Postigo; Isabel Arranz-Salas; Julia Alcaide; Maria Ramos-Fernandez; José Lozano; Hatim Boughanem; Pallavi Kompella; Manuel Macías-González

doi:10.3390/ijms24065488

8-Oxoguanine DNA Glycosylase 1 Upregulation as a Risk Factor for Obesity and Colorectal Cancer

Int J Mol Sci. 2023 Mar 13;24(6):5488. doi: 10.3390/ijms24065488.

Authors

Jesús Pilo^{1

2}, Libia Alejandra García-Flores^{1

2}, Mercedes Clemente-Postigo^{1

2

3

4

5}, Isabel Arranz-Salas^{6

7}, Julia Alcaide⁸, Maria Ramos-Fernandez⁹, José Lozano¹⁰, Hatim Boughanem^{1

2

3

11}, Pallavi Kompella^{1

2

12}, Manuel Macías-González^{1

2

3}

Affiliations

¹ Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, 29010 Malaga, Spain.
² Institute of Biomedical Research in Malaga (IBIMA)-Bionand Platform, University of Malaga, 29590 Malaga, Spain.
³ Spanish Biomedical Research Center in Physiopathology of Obesity and Nutrition (CIBERObn), Instituto de Salud Carlos III, 28029 Madrid, Spain.
⁴ Department of Cell Biology, Genetics, and Physiology, Faculty of Science, University of Malaga, 29590 Malaga, Spain.
⁵ Department of Cell Biology, Physiology and Immunology, Maimónides Biomedical Research Institute of Córdoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, 14004 Córdoba, Spain.
⁶ Division of Anatomical Pathology, Hospital Universitario Virgen de la Victoria, 29010 Malaga, Spain.
⁷ Department of Human Physiology, Human Histology, Anatomical Pathology and Physical Education, University of Malaga, 29010 Malaga, Spain.
⁸ Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria University Hospitals, IBIMA, 29010 Málaga, Spain.
⁹ Unidad de Gestion Clinica Cirugía General y del Aparato Digestivo, Virgen de la Victoria University, 29010 Malaga, Spain.
¹⁰ Department of Biochemistry and Molecular Biology, University of Malaga, 29010 Málaga, Spain.
¹¹ Unidad de Gestión Clinica Medicina Interna, Lipids and Atherosclerosis Unit, Maimonides Institute for Biomedical Research in Córdoba, Reina Sofia University Hospital, University of Córdoba, 14004 Córdoba, Spain.
¹² Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA.

Abstract

DNA damage has been extensively studied as a potentially helpful tool in assessing and preventing cancer, having been widely associated with the deregulation of DNA damage repair (DDR) genes and with an increased risk of cancer. Adipose tissue and tumoral cells engage in a reciprocal interaction to establish an inflammatory microenvironment that enhances cancer growth by modifying epigenetic and gene expression patterns. Here, we hypothesize that 8-oxoguanine DNA glycosylase 1 (OGG1)-a DNA repair enzyme-may represent an attractive target that connects colorectal cancer (CRC) and obesity. In order to understand the mechanisms underlying the development of CRC and obesity, the expression and methylation of DDR genes were analyzed in visceral adipose tissue from CRC and healthy participants. Gene expression analysis revealed an upregulation of OGG1 expression in CRC participants (p < 0.005) and a downregulation of OGG1 in normal-weight healthy patients (p < 0.05). Interestingly, the methylation analysis showed the hypermethylation of OGG1 in CRC patients (p < 0.05). Moreover, expression patterns of OGG1 were found to be regulated by vitamin D and inflammatory genes. In general, our results showed evidence that OGG1 can regulate CRC risk through obesity and may act as a biomarker for CRC.

Keywords: CRC; DNA repairs; OGG1; colorectal cancer; inflammation; methylation; obesity; repair genes.

MeSH terms

Colorectal Neoplasms* / genetics
DNA Damage
DNA Glycosylases* / genetics
DNA Glycosylases* / metabolism
DNA Repair / genetics
Humans
Obesity / complications
Obesity / genetics
Risk Factors
Tumor Microenvironment
Up-Regulation

Substances

8-hydroxyguanine
DNA Glycosylases
oxoguanine glycosylase 1, human

Grants and funding

This study was supported by the “Centro de Investigacion Biomédica en Red Fisiopatología de la Obesidad y Nutricion”, which is an initiative of the “Instituto de Salud Carlos III” (ISCIII) of Spain, financed by the European Regional Development Fund under “A way to make Europe”/“Investing in your future” (CB06/03), a grant from ISCIII (PI18/01399, PI21/00633), and a grant from the Consejeria Universidad, Investigacion e Innovacion Junta de Andalucia (PY20-01270). P.K. was supported by a Fulbright Usjunir Scholar Grant (JR-2021). HB is supported by a predoctoral fellowship (“Plan Propio IBIMA 2020 A.1 Contratos predoctorales”, Ref.: predoc20_002) and by a “Sara Borrell” postdoctoral contract (CD22/00053) from the Instituto de Salud Carlos III—Madrid (Spain), “Financiado por la Unión Europea—NextGenerationEU” y mediante el Plan de Recuperación, Transformación y Resiliencia. L.A.G.-F. was supported by a “Sara Borrell” postdoctoral contract (CD21/000131) from the Instituto de Salud Carlos III—Madrid (Spain). M.M.G. was the recipient of the Nicolas Monardes Programme from the “Servicio Andaluz de Salud, Junta de Andalucia”, Spain (RC-0001-2018 and C-0029-2014).