Oxidative DNA damage induces hypomethylation in a compromised base excision repair colorectal tumourigenesis

Furlan, Daniela; Trapani, Davide; Berrino, Enrico; Debernardi, Carla; Panero, Mara; Libera, Laura; Sahnane, Nora; Riva, Cristina; Tibiletti, Maria Grazia; Sessa, Fausto; Sapino, Anna; Venesio, Tiziana

doi:10.1038/bjc.2017.9

Cited by 18 publications

(25 citation statements)

References 46 publications

(59 reference statements)

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“…Further, recent studies disclosed the role of MTH1, which prevents incorporation of oxidized purines into DNA, in malignant transformation [143]. However, high expression of MTH1 has been observed in many human malignancies [82,83], including CRC, where the enzyme bolster survival of the malignant cells. These seeming discrepancies may be explainable by the versatile role of oxidative DNA damage in carcinogenesis: its higher extent may trigger a malignant transformation in very early stages, whereas in developed tumors, its lower level (or efficient BER) may give additional survival/growth advantage to cancer cells [144].…”

Section: Discussionmentioning

confidence: 99%

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

Vodička

Urbanová

Makovický

et al. 2020

IJMS

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Oxidative stress with subsequent premutagenic oxidative DNA damage has been implicated in colorectal carcinogenesis. The repair of oxidative DNA damage is initiated by lesion-specific DNA glycosylases (hOGG1, NTH1, MUTYH). The direct evidence of the role of oxidative DNA damage and its repair is proven by hereditary syndromes (MUTYH-associated polyposis, NTHL1-associated tumor syndrome), where germline mutations cause loss-of-function in glycosylases of base excision repair, thus enabling the accumulation of oxidative DNA damage and leading to the adenoma-colorectal cancer transition. Unrepaired oxidative DNA damage often results in G:C>T:A mutations in tumor suppressor genes and proto-oncogenes and widespread occurrence of chromosomal copy-neutral loss of heterozygosity. However, the situation is more complicated in complex and heterogeneous disease, such as sporadic colorectal cancer. Here we summarized our current knowledge of the role of oxidative DNA damage and its repair on the onset, prognosis and treatment of sporadic colorectal cancer. Molecular and histological tumor heterogeneity was considered. Our study has also suggested an additional important source of oxidative DNA damage due to intestinal dysbiosis. The roles of base excision repair glycosylases (hOGG1, MUTYH) in tumor and adjacent mucosa tissues of colorectal cancer patients, particularly in the interplay with other factors (especially microenvironment), deserve further attention. Base excision repair characteristics determined in colorectal cancer tissues reflect, rather, a disease prognosis. Finally, we discuss the role of DNA repair in the treatment of colon cancer, since acquired or inherited defects in DNA repair pathways can be effectively used in therapy.

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Section: Discussionmentioning

confidence: 99%

“…Less information is currently available on MTH1 nuclease with regard to sporadic CRC. High expression of MTH1 has been observed in many human malignancies [82,83], including CRC, where the enzyme bolsters survival of the malignant cells and acts therefore in procarcinogenic manner.…”

Section: Sporadic Colorectal Cancermentioning

confidence: 99%

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

Vodička

Urbanová

Makovický

et al. 2020

IJMS

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“…The interruption of BER leads to cancer through accumulation of oxidative DNA damage caused that has been observed in MUTYH-related polyposis (MAP). MAP is a hereditary colorectal cancer syndrome that is caused by adenoma and cancers with a cumulative 8-Oxo guanine , which causes mutation in the mutY homolog E. coli (MUTYH) gene ( Figure 2) [38]. The MUTYH gene is located on the short arm of chromosome 1, and its map is P34.3_P32.11 and is about 2.11 kilobases long and consists of 16 exons.…”

Section: Involvement Of Certain Genesmentioning

confidence: 99%

Epigenetic profiling of MUTYH, KLF6, WNT1 and KLF4 genes in carcinogenesis and tumorigenesis of colorectal cancer

Babaei¹,

Khaksar²,

Zeinali³

et al. 2019

BioMedicine

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Colorectal cancer (CRC) is distinguished by epigenetic elements like DNA methylation, histone modification, histone acetylation and RNA remodeling which is related with genomic instability and tumor initiation. Correspondingly, as a main epigenetic regulation, DNA methylation has an impressive ability in order to be used in CRC targeted therapy. Meaningly, DNA methylation is identified as one of most important epigenetic regulators in gene expression and is considered as a notable potential driver in tumorigenesis and carcinogenesis through gene-silencing of tumor suppressors genes. Abnormal methylation situation, even in the level of promoter regions, does not essentially change the gene expression levels, particularly if the gene was become silenced, leaving the mechanisms of methylation without any response. According to the methylation situation which has a strong eagerness to be highly altered on CpG islands in carcinogenesis and tumorigenesis, considering its epigenetic fluctuations in finding new biomarkers is of great importance. Modifications in DNA methylation pattern and also enrichment of methylated histone signs in the promoter regions of some certain genes like MUTYH, KLF4/6 and WNT1 in different signaling pathways could be a notable key contributors to the upregulation of tumor initiation in CRC. These epigenetic alterations could be employed as a practical diagnostic biomarkers for colorectal cancer. In this review, we will be discuss these fluctuations of MUTYH, KLF4/6 and WNT1 genes in CRC.

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“…This could contribute to gene mutations involved in cancer initiation [42]. Oxidative stress can also lead to hypermethylation of tumor suppressors and hypomethylation of oncogenes, which implies its role in cancer initiation [43,44].…”

Section: Ros/oxidative Stress-related Mechanism In Bcamentioning

confidence: 99%

Current updates on the role of reactive oxygen species in bladder cancer pathogenesis and therapeutics

et al. 2020

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Bladder cancer (BCa) is the fourth most common urological malignancy in the world, it has become the costliest cancer to manage due to its high rate of recurrence and lack of effective treatment modalities. As a natural byproduct of cellular metabolism, reactive oxygen species (ROS) have an important role in cell signaling and homeostasis. Although up-regulation of ROS is known to induce tumorigenesis, growing evidence suggests a number of agents that can selectively kill cancer cells through ROS induction. In particular, accumulation of ROS results in oxidative stress-induced apoptosis in cancer cells. So, ROS is a double-edged sword. A modest level of ROS is required for cancer cells to survive, whereas excessive levels kill them. This review summarizes the up-to-date findings of oxidative stress-regulated signaling pathways and transcription factors involved in the etiology and progression of BCa and explores the possible therapeutic implications of ROS regulators as therapeutic agents for BCa. Keywords Reactive oxygen species • Oxidative stress • Bladder cancer • Apoptosis • Therapeutics Abbreviations ALKBH8 Alkylated DNA repair protein alkB homolog 8 ASK1 Apoptosis signal-regulating kinase 1 BCa Bladder cancer Egr-1 Early growth response gene-1 ERK Extracellular signal-regulated kinase FGFR3 Fibroblast growth factor receptor 3 G6PD Glucose-6-phosphate dehydrogenase HDACI Histone deacetylase inhibitor JNK c-JunN-terminal kinase LCA Licochalcone A LTB4R2 Leukotriene B4 receptor 2 gene MIBC Muscle invasive bladder cancer MKPs MAP kinase phosphatases MMP9 Matrix metalloproteinase-9 MT-CYB Mitochondrial cytochrome b NRF2 Nuclear factor erythroid 2-related factor 2 ROS Reactive oxygen species SPARC Serum protein acidic and rich in cysteine TM4SF1 Transmembrane-4-L-six-family-1 VEGF Vascular endothelial growth factor * F.

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Oxidative DNA damage induces hypomethylation in a compromised base excision repair colorectal tumourigenesis

Cited by 18 publications

References 46 publications

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

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

Epigenetic profiling of MUTYH, KLF6, WNT1 and KLF4 genes in carcinogenesis and tumorigenesis of colorectal cancer

Current updates on the role of reactive oxygen species in bladder cancer pathogenesis and therapeutics

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