Dataset Information

MiR-944/CISH mediated inflammation via STAT3 is involved in oral cancer malignance by cigarette smoking.

ABSTRACT: The cytokine-inducible Src homology 2-containing protein (CISH) is an endogenous suppressors of signal transduction and activator of transcription (STAT) and acts as a key negative regulator of inflammatory cytokine responses. Downregulation of CISH has been reported to associate with increased activation of STAT and enhanced inflammatory pathways. However, whether microRNAs (miRNAs) play a crucial role in CISH/STAT regulation in oral squamous cell carcinoma (OSCC) remains unknown. The expression of CISH on OSCC patients was determine by quantitative real-time PCR (qRT-PCR) and immunohistochemistry. Specific targeting by miRNAs was determined by software prediction, luciferase reporter assay, and correlation with target protein expression. The functions of miR-944 and CISH were accessed by transwell migration and invasion analyses using gain- and loss-of-function approaches. Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR were used to evaluate the pro-inflammation cytokines expression under the miR-944, CISH, NNK or combinations treatment. We found that the CISH protein, which modulates STAT3 activity, as a direct target of miR-944. CISH protein was significantly down-regulated in OSCC patients and cell lines and its level was inversely correlated with miR-944 expression. The miR-944-induced STAT3 phosphorylation, pro-inflammation cytokines secretion, migration and invasion were abolished by CISH restoration, suggesting that the oncogenic activity of miR-944 is CISH dependent. Furthermore, tobacco extract (NNK) may contribute to miR-944 induction and STAT3 activation. Antagomir-mediated inactivation of miR-944 prevented the NNK-induced STAT3 phosphorylation and pro-inflammation cytokines secretion. Altogether, these data demonstrate that NNK-induced miR944 expression plays an important role in CISH/STAT3-mediated inflammatory response and activation of tumor malignancy.

SUBMITTER: Peng HY

PROVIDER: S-EPMC7505767 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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MiR-944/CISH mediated inflammation via STAT3 is involved in oral cancer malignance by cigarette smoking.

Peng Hsuan-Yu HY Hsiao Jenn-Ren JR Chou Sung-Tau ST Hsu Yuan-Ming YM Wu Guan-Hsun GH Shieh Yi-Shing YS Shiah Shine-Gwo SG

Neoplasia (New York, N.Y.) 20200919 11

The cytokine-inducible Src homology 2-containing protein (CISH) is an endogenous suppressors of signal transduction and activator of transcription (STAT) and acts as a key negative regulator of inflammatory cytokine responses. Downregulation of CISH has been reported to associate with increased activation of STAT and enhanced inflammatory pathways. However, whether microRNAs (miRNAs) play a crucial role in CISH/STAT regulation in oral squamous cell carcinoma (OSCC) remains unknown. The expressio ...[more]

PMID: 32961483

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Project description:BackgroundElectronic cigarettes (ECs) have been widely used by young individuals in the U.S. while being considered less harmful than conventional tobacco cigarettes. However, ECs have increasingly been regarded as a health risk, producing detrimental chemicals that may cause, combined with poor oral hygiene, substantial inflammation in gingival and subgingival sites. In this paper, we first report that EC smoking significantly increases the odds of gingival inflammation. Then, through mediation analysis, we seek to identify and explain the mechanism that underlies the relationship between EC smoking and gingival inflammation via the oral microbiome.MethodsWe collected saliva and subgingival samples from 75 EC users and 75 non-users between 18 and 34 years in age and profiled their microbial compositions via 16S rRNA amplicon sequencing. We conducted raw sequence data processing, denoising and taxonomic annotations using QIIME2 based on the expanded human oral microbiome database (eHOMD). We then created functional annotations (i.e., KEGG pathways) using PICRUSt2.ResultsWe found significant increases in α-diversity for EC users and disparities in β-diversity between EC users and non-users. We also found significant disparities between EC users and non-users in the relative abundance of 36 microbial taxa in the saliva site and 71 microbial taxa in the subgingival site. Finally, we found that 1 microbial taxon in the saliva site and 18 microbial taxa in the subgingival site significantly mediated the effects of EC smoking on gingival inflammation. The mediators on the genus level, for example, include Actinomyces, Rothia, Neisseria, and Enterococcus in the subgingival site. In addition, we report significant disparities between EC users and non-users in the relative abundance of 71 KEGG pathways in the subgingival site.ConclusionsThese findings reveal that continued EC use can further increase microbial dysbiosis that may lead to periodontal disease. Our findings also suggest that continued surveillance for the effect of ECs on the oral microbiome and its transmission to oral diseases is needed.

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.

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.

Dataset Information

MiR-944/CISH mediated inflammation via STAT3 is involved in oral cancer malignance by cigarette smoking.

Publications

MiR-944/CISH mediated inflammation via STAT3 is involved in oral cancer malignance by cigarette smoking.

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