8-hydroxy-2--deoxyguanosine and Squamous-Cell-Carcinoma-of-Head-and-Neck

To investigate how Fusobacterium nucleatum (Fn) promotes oxidative stress and mediates proliferation and autophagy in hypopharyngeal squamous cell carcinoma (HPSCC).. The prognosis for 82 HPSCC cases was retrospectively analyzed. HPSCC cell line FaDu was co-cultured with Fn. Knockdown of NUDT1 (shNUDT1 group) was done after observing DNA damage response. CCK8 and tumorigenesis assays for proliferation observation, mitochondria ROS (MitoROS) measurement to examine intracellular oxidative stress, and ELISA to analyze concentration of 8-oxo-2'-deoxyguanosine (8-oxo-dG) in cells. Dual-luciferase reporter assays clarified miR-361-3p connection with NUDT1. Autophagy flow was observed using electron microscopy and related proteins.. Fn was highly associated with NUDT1. The shNUDT1 group experienced lower proliferation compared with normal FaDu (NC group) in vivo and in vitro. The shNUDT1 group showed 8-oxo-dG and γH2AX to be elevated. Intracellular ROS decreased in shNUDT1Fn group when compared to Fn group. Upregulating miR-361-3p could suppress NUDT1 expression and downstream proliferation and autophagy. Fn modulated miR-361-3p via OH. Higher Fn in HPSCC patients suggests poorer prognosis. NUDT1 might affect cell proliferation and autophagy and modulate DNA damage response. The oxidative stress induced miR-361-3p/NUDT1 axis is first introduced in microbiome-carcinoma research.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Autophagy; Cell Line, Tumor; Cell Proliferation; Fusobacterium nucleatum; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Humans; Hydrogen Peroxide; MicroRNAs; Oxidative Stress; Reactive Oxygen Species; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck

To determine whether the breast cancer susceptibility gene 1 (BRCA1) regulates oxidative damage in oral cancer cells by interacting with nuclear factor erythroid 2-like 2 (NRF2).. The BRCA1 gene was silenced in CAL-27 and DOK cells using specific shRNA, and NRF2 was activated with sulforaphane. The expression levels of BRCA1, NRF2 and its target genes were assessed by quantitative real-time polymerase chain reaction and western blotting. Cell counting kit-8 assay was used to detect cell proliferation, apoptosis was detected by flow cytometry, and 8-OXo-2'-deoxyguanosine level was measured by enzyme-linked immunosorbent assay. The expression of BRCA1 and NRF2 in patients with oral leukoplakia and oral squamous cell carcinoma were evaluated by immunohistochemistry.. BRCA1 knockdown downregulated NRF2 and its target genes, increased proliferation rates, reduced apoptosis, and increased 8-OXo-2'-deoxyguanosine levels compared to the control. Activation of NRF2 by sulforaphane significantly upregulated NRF2 levels in the BRCA1-depleted cells, and restored proliferation, apoptosis and 8-OXo-2'-deoxyguanosine level in a dose-dependent manner. Compared with patients with leukoplakia, BRCA1 and NRF2 expression were increased in patients with oral squamous cell carcinoma.. BRCA1 depletion increases oxidative damage and promotes the malignant phenotype, which may eventually promote oral carcinogenesis. The NRF2-activator sulforaphane is a potential chemo-preventive agent for oral cancer.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Apoptosis; BRCA1 Protein; Female; Humans; Isothiocyanates; Mouth Neoplasms; NF-E2-Related Factor 2; Oxidative Stress; Squamous Cell Carcinoma of Head and Neck; Sulfoxides

8-Hydroxy-2'-deoxyguanosine is a biomolecule associated with DNA damage. We evaluated oxidative stress and DNA damage in patients with laryngeal cancer by measuring 8-hydroxy-2'-deoxyguanosine levels.. This study enrolled 117 subjects, including 64 controls and 53 patients who had benign vocal cord lesions or laryngeal cancer. The benign excised lesions, tumor tissue, noncancerous laryngeal tissue, blood, and urine were subjected to high-performance liquid chromatography, and 8-hydroxy-2'-deoxyguanosine levels were compared between groups.. Blood and urine 8-hydroxy-2'-deoxyguanosine levels in patients with laryngeal carcinoma were significantly higher than in the controls ( P = .00002, P = .00001). The 8-hydroxy-2'-deoxyguanosine level was significantly higher in tumor tissues than in non-tumor tissue and benign vocal cord lesion tissues ( P = .00002, P = .000001).. We determined that laryngeal cancer was associated with oxidative stress, which may be quantified by measuring 8-hydroxy-2'-deoxyguanosine. For a patient with a suspicious laryngeal lesion, 8-hydroxy-2'-deoxyguanosine levels in blood and urine can provide advance information about the likely diagnosis.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Carcinoma, Squamous Cell; Case-Control Studies; Chromatography, High Pressure Liquid; Deoxyguanosine; DNA; DNA Damage; Female; Head and Neck Neoplasms; Humans; Laryngeal Neoplasms; Laryngectomy; Male; Middle Aged; Oxidative Stress; Smoking; Squamous Cell Carcinoma of Head and Neck