Cigarette smoking induces the activation of RIP2/caspase-12/NF-κB axis in oral squamous cell carcinoma
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ABSTRACT:
SUBMITTER: Qian Y
PROVIDER: S-EPMC9639427 | biostudies-literature | 2022 Jan
REPOSITORIES: biostudies-literature
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Project description:Ubiquitin D (UBD) is highly upregulated in many cancers, and plays a pivotal role in the pathophysiological processes of cancers. However, its roles and underlying mechanisms in oral squamous cell carcinoma (OSCC) are still unclear. In the present study, we investigated the role of UBD in patients with OSCC. Quantitative real-time polymerase chain reaction and Western blot were used to measure the expression of UBD in OSCC tissues. Immunohistochemistry assay was used to detect the differential expressions of UBD in 244 OSCC patients and 32 cases of normal oral mucosae. In addition, CCK-8, colony formation, wound healing and Transwell assays were performed to evaluate the effect of UBD on the cell proliferation, migration, and invasion in OSCC. Furthermore, a xenograft tumor model was established to verify the role of UBD on tumor formation in vivo. We found that UBD was upregulated in human OSCC tissues and cell lines and was associated with clinical and pathological features of patients. Moreover, the overexpression of UBD promoted the proliferation, migration and invasion of OSCC cells; however, the knockdown of UBD exerted the opposite effects. In this study, our results also suggested that UBD promoted OSCC progression through NF-κB signaling. Our findings indicated that UBD played a critical role in OSCC and may serve as a prognostic biomarker and potential therapeutic target for OSCC treatment.
| S-EPMC8334351 | biostudies-literature
Project description:Caspase 14 is one of the latter discovered members of the caspase enzyme family and, although sharing sequence homologies with the other caspases, it is not involved in apoptosis. Together with its co-factor filaggrin, it plays an important role in skin barrier formation. It is already known that caspase 14 proteins are reduced during neoplastic dedifferentiation in cervical intraepithelial neoplasms and in invasive cervical carcinomas. Oral squamous carcinoma tissues have not been systematically evaluated for caspase 14 expression yet. Formalin-fixed and paraffin-embedded samples from oral squamous carcinomas (n = 36 tumours from 34 patients), metastases (n = 15) and controls (leukoplakia, n = 10) were analysed by immunohistochemistry. In carcinomas, human papilloma virus (HPV) infection was tested by PCR. Here we demonstrate that, in oral epithelia, caspase 14 is expressed mainly by cells of the intermediate and superficial cell layers while filaggrin is expressed only in keratinising foci in leukoplakia. Caspase 14 and filaggrin are co-localised. In invasive oral carcinomas, reduced expression of caspase 14 was detectable in 47 % of tumours but was not associated with keratinisation, tumour differentiation or HPV infection. Filaggrin was detectable in a subfraction of tumours (56 %) and was restricted to keratinising areas of the carcinomas. In summary, in contrast to cervical carcinomas, partial loss of caspase 14 is not associated with dedifferentiation in neoplastic lesions of the oral mucosa or HPV infection.
| S-EPMC3824792 | biostudies-literature
Project description:Caspase-8 (CASP8) is a key controller of apoptosis, and its deregulation is crucially involved in carcinogenesis. The aim of the present study was to evaluate the function of CASP8 polymorphisms in oral squamous carcinoma (OSCC) by evaluating the risk associated with three single-nucleotide polymorphisms (SNPs) in a case-control study in a Han Chinese patient population. A total of 505 individuals with clinically diagnosed OSCC and 507 healthy controls were tested for the three SNPs rs3834129, rs13016963 and rs1045485, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing analysis. After adjusting for other confounders, the genotype frequencies of CASP8 -652 6N ins/del promoter polymorphism (rs3834129) were found to be lower in patients with OSCC compared with normal subjects. No significant difference was detected in the genotype frequencies of rs13016963 between the patients and control subjects. However, the AA genotype frequency of rs1306963 was associated with OSCC as a risk factor among non-smokers and non-drinkers. For CASP8, rs1045485 was not present in any of the patients with OSCC or control subjects. These results suggest that the del allele of rs3834129 may play a protective role in the tumorigenesis of OSCC and may be useful as a genetic susceptibility marker for OSCC in the population studied.
| S-EPMC4665542 | biostudies-literature
Project description:BackgroundThe goal of the study was to investigate whether cigarette smoking alters oral and nasal microbial diversity, composition, and structure. Twenty-three current smokers and 20 never smokers were recruited. From each subject, nine samples including supra and subgingiva plaque scrapes, saliva, swabs from five soft oral tissue sites, and one nasal swab from both the anterior nares were collected. 16S rRNA V3-V4 region was sequenced for microbial profiles.ResultsWe found that alpha diversity was lower in smokers than in nonsmokers in the buccal mucosa, but in other sample sites, microbial diversity and composition were not significantly different by smoking status. Microbial profiles differed significantly among eight oral sites.ConclusionsThis study investigates the effect of cigarette smoking on different sites of the oral cavity and shows a potential effect of cigarette smoking on the buccal mucosa microbiota. The marked heterogeneity of the oral microbial ecosystem that we found may contribute to the stability of the oral microbiota in most sites when facing environmental perturbations such as that caused by cigarette smoking.
| S-EPMC5240432 | biostudies-literature
Project description:The oral microbiota has been observed to be influenced by cigarette smoking and linked to several human diseases. However, research on the effect of cigarette smoking on the oral microbiota has not been systematically conducted in the Chinese population. We profiled the oral microbiota of 316 healthy subjects in the Chinese population by 16S rRNA gene sequencing. The alpha diversity of oral microbiota was different between never smokers and smokers (P = 0.002). Several bacterial taxa were first reported to be associated with cigarette smoking by LEfSe analysis, including Moryella (q = 1.56E-04), Bulleidia (q = 1.65E-06), and Moraxella (q = 3.52E-02) at the genus level and Rothia dentocariosa (q = 1.55E-02), Prevotella melaninogenica (q = 8.48E-08), Prevotella pallens (q = 4.13E-03), Bulleidia moorei (q = 1.79E-06), Rothia aeria (q = 3.83E-06), Actinobacillus parahaemolyticus (q = 2.28E-04), and Haemophilus parainfluenzae (q = 4.82E-02) at the species level. Two nitrite-producing bacteria that can increase the acidity of the oral cavity, Actinomyces and Veillonella, were also enriched in smokers with FDR-adjusted q-values of 3.62E-06 and 1.10E-06, respectively. Notably, we observed that two acid production-related pathways, amino acid-related enzymes (q = 6.19E-05) and amino sugar and nucleotide sugar metabolism (q = 2.63E-06), were increased in smokers by PICRUSt analysis. Finally, the co-occurrence analysis demonstrated that smoker-enriched bacteria were significantly positively associated with each other and were negatively correlated with the bacteria decreased in smokers. Our results suggested that cigarette smoking may affect oral health by creating a different environment by altering bacterial abundance, connections among oral microbiota, and the microbiota and their metabolic function.
| S-EPMC8195269 | biostudies-literature
Project description:BackgroundHeavy tobacco smoking, a hallmark feature of lung cancer, is drastically predominant in Middle Eastern populations. The precise links between nicotine dependence and the functional contribution of the oral microbiota remain unknown in these populations.MethodsWe evaluated the composition and functional capabilities of oral microbiota with relation to cigarette smoking in 105 adults through shotgun metagenomics using buccal swabs.ResultsThe oral microbiota composition in our study subjects was dominated by the phyla Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes, in addition to the genera Prevotella and Veillonella, similar to previously described westernized cohorts. Furthermore, the smoker's oral microbiota represented a significant abundance of Veillonella dispar, Leptotrichia spp. and Prevotella pleuritidis when compared to non-smokers. Within the smoking groups, differential relative abundance testing unveiled relative abundance of Streptobacillus hongkongensis, Fusobacterium massiliense, Prevotella bivia in high nicotine dependent compared to low nicotine dependent profiles based on Fagerström Test for Nicotine Dependence. Functional profiling showed marked differences between smokers and non-smokers. Smokers exhibited an enrichment of Tricarballylate utilization and Lactate racemization when compared to the non-smokers. According to their nicotine dependence, enrichment of Xanthosine utilization, p-Aminobenzoyl-Glutamate utilization, and multidrug efflux pump in Campylobacter jejuni biosynthesis modules were detected in the high nicotine dependent group.ConclusionsThese compositional and functional differences may provide critical insight on how variations in the oral microbiota could predispose to respiratory illnesses and smoke cessation relapse in cigarette smokers. In particular, the observed enrichment of Fusobacterium and Prevotella in the oral microbiota possibly suggests an intriguing linkage to gut and lung cancers.
| S-EPMC7653996 | biostudies-literature
Project description:ObjectivesCigarette smoke exposure is a significant risk factor in the development of otitis media (OM). Nuclear factor kappa B (NF-kappa B) is a ubiquitous transcription factor known to mediate cigarette smoke effects on gene regulation in multiple cell types. The MUC5B mucin gene contains several putative NF-kappa B sites in its promoter and is the predominant mucin expressed in human OM. We hypothesized that in vitro stimulation of a recently developed model system, murine middle ear epithelial cells (MEEC), with cigarette smoke condensate (CSC) activates NF-kappa B and subsequently induces Muc5b gene expression.MethodsLuciferase reporter assays, electromobility shift assays (EMSA), and quantitative microplate transcription factor assays (TFA) were performed to evaluate NF-kappaB activation with CSC in immortalized murine MEEC (mMEEC). Reverse transcriptase polymerase chain reaction (RT-PCR) assays and quantitative real time RT-PCR were performed to determine whether time course CSC stimulation upregulates Muc5b mRNA levels in differentiated mMEEC. Luciferase reporter assays were performed to determine whether CSC activates the Muc5b promoter.ResultsReporter assays, EMSA, and TFA demonstrated three- to five-fold dose-dependent activation of NF-kappa B with CSC in mMEEC. CSC stimulation likewise increased Muc5b mRNA abundance and induced reporter activity 1.8- to 4.8-fold in plasmids containing -556 and -255 base pairs upstream of the Muc5b transcriptional start site in mMEEC.ConclusionsCSC activates NF-kappaB in immortalized MEEC. Furthermore, this activation correlates with CSC-induced Muc5b promoter activation and gene expression. Taken together, these results hint that much as in lung cells, the activation of mucins by cigarette smoke is mediated in part by NF-kappa B.
| S-EPMC2692718 | biostudies-literature
Project description:BackgroundCigarette smoking is a common risk factor for diseases and cancers. Oral microbiota is also associated with diseases and cancers. However, little is known about the impact of cigarette smoking on the oral microbiota, especially among ethnic minority populations.MethodsWe investigated cigarette smoking in relationship with the oral microbiota in a large population of predominately low-income and African-American participants. Mouth rinse samples were collected from 1616 participants within the Southern Community Cohort Study, including 592 current-smokers, 477 former-smokers and 547 never-smokers. Oral microbiota was profiled by 16S ribosomal RNA gene deep sequencing.ResultsCurrent-smokers showed a different overall microbial composition from former-smokers (p=6.62×10-7) and never-smokers (p=6.00×10-8). The two probiotic genera, Bifidobacterium and Lactobacillus, were enriched among current-smokers when compared with never-smokers, with Bonferroni-corrected p values (PBonferroni ) of 1.28×10-4 and 5.89×10-7, respectively. The phylum Actinobacteria was also enriched in current-smokers when compared with never-smokers, with a median relative abundance of 12.35% versus 9.36%, respectively, and with a PBonferroni =9.11×10-11. In contrast, the phylum Proteobacteria was depleted in current smokers (PBonferroni =5.57×10-13), with the relative abundance being almost three times that of never-smokers (7.22%) when compared with that of current-smokers (2.47%). Multiple taxa within these two phyla showed differences in abundance/prevalence between current-smokers and never-smokers at PBonferroni <0.05. The differences in the overall microbial composition and abundance/prevalence of most taxa were observed among both African-Americans and European-Americans. Meanwhile, such differences were not observed between former-smokers and never-smokers.ConclusionSmoking has strong impacts on oral microbial community, which was recovered after smoking cessation.
| S-EPMC6913090 | biostudies-literature
Project description:Oral squamous cell carcinoma (OSCC) is a subtype of head and neck cancer that arises in the multilayered epithelia of the mouth and lips. Although inactivating mutations in CASP8 are frequently found in human OSCC their role in the disease is unknown. To investigate this, we deleted Casp8 in the oral epithelium of adult mice. Loss of Caspase-8 resulted in defects in the tongue epithelial barrier and triggered a neutrophil-rich immune infiltrate distinct from that observed on epidermal Casp8 deletion. Oral Casp8 deletion led to activation of autophagy. Inhibition of autophagy partially rescued epithelial integrity in Casp8-/- mice, while induction of autophagy in wild type mice resulted in oral barrier defects and excessive neutrophil infiltration. On treatment with the carcinogen 4-nitroquinoline-1-oxide Casp8-/- mice showed increased susceptibility to developing oral tumors. Depletion of neutrophils reduced tumor incidence, which correlated with a reduction in reactive oxygen species and decreased epithelial DNA damage. Our findings establish a functional link between epithelial integrity, autophagy, and the tumor immune microenvironment, placing Caspase-8 at the center of these processes.
| S-EPMC11648635 | biostudies-literature
Project description:The NF-κB family of transcription factors is essential for promoting cell proliferation and preventing cell apoptosis. We have previously shown that Andrographolide (Andro) isolated from an herbal plant, Andrographis paniculata, covalently modifies reduced cysteine(62) in the oligonucleotide binding pocket of p50 for inhibition of NF-κB activation. Here we report that Andro, but not its inactive structural analog 4H-Andro, potently suppressed squamous cell carcinogenesis induced by 7,12-dimethyl-1,2-benzanthracene (DMBA) in the hamster model of cheek buccal pouch. Compared with 4H-Andro, Andro reduced phosphorylation of p65 (Ser536) and IκBα (Ser32/36) for inhibiting aberrant NF-κB activation, suppressed c-Myc and cyclin D1 expression and attenuated neoplastic cell proliferation, promoted cancerous cell apoptosis, and mitigated tumor-induced angiogenesis. Consistently, Andro retarded growth, decreased proliferation, and promoted apoptosis of Tb cells, a human tongue squamous cell carcinoma cell line, in time- and dose-dependent manners, with concomitant reduction of the expression of NF-κB targeting molecules in vitro. Our results thus demonstrate that NF-κB activation plays important roles in the pathogenesis of chemically induced squamous cell carcinoma. By inhibition of aberrant NF-κB activation, Andro treats chemically induced oral squamous cell carcinogenesis.
| S-EPMC6761731 | biostudies-literature