A combined epigenome- and transcriptome-wide association study of the oral masticatory mucosa assigns CYP1B1 a central role for epithelial health in smokers
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ABSTRACT:
PROVIDER: PRJNA561777 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10027356.fastq.gz | Fastqsanger.gz | |||
| SRR10027357.fastq.gz | Fastqsanger.gz | |||
| SRR10027358.fastq.gz | Fastqsanger.gz | |||
| SRR10027359.fastq.gz | Fastqsanger.gz | |||
| SRR10027360.fastq.gz | Fastqsanger.gz |
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Project description:Healthy ex vivo biopsies from masticatory mucosa from 17 current and 21 never smokers were analysed using whole transcriptome RNA sequencing (16 mio reads/sample), showing significantly increased expression of CYP1B1 in smokers compared to non-smokers (p = 2.2 × 10−14), together with 13 significantly upregulated transcripts. Six transcripts were significantly downregulated.
2019-08-24 | GSE136262 | GEO
Project description:BackgroundThe oral mucosa has an important role in maintaining barrier integrity at the gateway to the gastrointestinal and respiratory tracts. Smoking is a strong environmental risk factor for the common oral inflammatory disease periodontitis and oral cancer. Cigarette smoke affects gene methylation and expression in various tissues. This is the first epigenome-wide association study (EWAS) that aimed to identify biologically active methylation marks of the oral masticatory mucosa that are associated with smoking.ResultsEx vivo biopsies of 18 current smokers and 21 never smokers were analysed with the Infinium Methylation EPICBeadChip and combined with whole transcriptome RNA sequencing (RNA-Seq; 16 mio reads per sample) of the same samples. We analysed the associations of CpG methylation values with cigarette smoking and smoke pack year (SPY) levels in an analysis of covariance (ANCOVA). Nine CpGs were significantly associated with smoking status, with three CpGs mapping to the genetic region of CYP1B1 (cytochrome P450 family 1 subfamily B member 1; best p = 5.5 × 10-8) and two mapping to AHRR (aryl-hydrocarbon receptor repressor; best p = 5.9 × 10-9). In the SPY analysis, 61 CpG sites at 52 loci showed significant associations of the quantity of smoking with changes in methylation values. Here, the most significant association located to the gene CYP1B1, with p = 4.0 × 10-10. RNA-Seq data showed significantly increased expression of CYP1B1 in smokers compared to non-smokers (p = 2.2 × 10-14), together with 13 significantly upregulated transcripts. Six transcripts were significantly downregulated. No differential expression was observed for AHRR. In vitro studies with gingival fibroblasts showed that cigarette smoke extract directly upregulated the expression of CYP1B1.ConclusionThis study validated the established role of CYP1B1 and AHRR in xenobiotic metabolism of tobacco smoke and highlights the importance of epigenetic regulation for these genes. For the first time, we give evidence of this role for the oral masticatory mucosa.
| S-EPMC6647091 | biostudies-literature
Project description:Long non-coding Rnas (lncRNAs) can act as oncogenes or tumor suppressors to regulate cancer development. We found that CYP1B1-AS1 was down-regulated in breast cancer tissues and correlated with the prognosis of patients. Lentiviral vectors were used to overexpress CYP1B1-AS1 in MCF7 cells, and the target proteins bound to CYP1B1-AS1 were detected by pulldown assay and mass spectrometry. The function of CYP1B1-AS1 is unknown. Our study revealed the molecular mechanism of CYP1B1-AS1 inhibiting breast cancer proliferation in breast cancer, and provided a new strategy for the treatment of breast cancer targeting lncRNA.
2023-10-24 | PXD037317 | Pride
Project description:Medwakh smoking has radically expanded among the youth in the Middle East and around the world. The rising popularity of medwakh/dokha usage is linked to the onset of several chronic illnesses including cardiovascular diseases and cancers. The present study aims to elucidate changes in the salivary proteome of medwakh smokers and explore the resultant pathological alterations in comparison to non-smokers. Statistical measurements reveal significant alterations in the abundance of 74 protein profiles in medwakh smokers compared to non-smokers. Medwakh smoking affected proteins with roles in cell anchorage and adhesion (FERMT3, CAPZA2, ACTN1, TLN1), immune responses, and inflammation (CFI, PSME2, S100A12, CHI3L1, HRG, RNASE2, ORM2), oxidative and anti-oxidative stress responses (NCF4, ERP 29, AKRA1, NADPH, NCF1B) and various cell metabolic processes (G6PD, HEXB, HK3, EEF1A1, PYGL, UGP2, EEF1A1). In our investigation, several novel proteins such as CFI, RNASE2, ORM2, NQO2, SULT1A1, TSN, and UBA1 were also discovered. These proteins play key roles in the initiation of various pathologies and are unique in medwakh smokers. The high significant increase in the abundance of involucrin suggests an alarming squamous cell differentiation in medwakh smokers. In addition, various pathways related to mitochondrial damage, oxidative burst, cell adhesion, migration, differentiation, and proliferation were significantly altered in medwakh smokers. The knowledge gained would help to elucidate the adverse effects of medwakh smoking, especially among adolescents, raising awareness of plausible health hazards, thereby improving the quality of life.
2025-05-06 | PXD045901 | Pride
Project description:Coxiella burnetii (Cb), the causative agent of Q fever, replicates within host macrophages by modulating immune responses through poorly understood mechanisms. Long non-coding RNAs (lncRNAs) are crucial yet underexplored regulators of inflammation, particularly in Cb pathogenesis. Employing a comparative transcriptomic analysis of THP-1 macrophages infected with 16 different microbes, we dissected a core set of immune-responsive lncRNAs such as MAILR, LINC01215, PACER, and MROCKI-common to human anti-pathogen responses, and distinguished them from lncRNAs specifically altered at early (1 h) time points in individual infections. In particular, our approach unveiled lncRNA CYP1B1-AS1 as specifically upregulated in a spatiotemporal manner along with CYP1B1 in cis during Cb infection. Promoter assays confirmed their co-regulation via a shared bidirectional promoter, while aryl hydrocarbon receptor (AHR)-lucia luciferase and nuclear translocation assays demonstrated that Cb infection activates AHR, driving their transcription. Knockdown of CYP1B1-AS1 or CYP1B1 alone disrupted mitochondrial homeostasis, increased ROS and mitochondrial dysfunction, and exacerbated apoptosis during infection. These findings position the CYP1B1-AS1/CYP1B1 axis as a key regulator of mitochondrial homeostasis under AHR signaling, supporting an intracellular environment that benefits Cb replication. Our results highlight the critical roles of lncRNAs in immune regulation and provide a valuable resource for future lncRNA research.
2025-07-14 | GSE292317 | GEO
Project description:Upregulation of Expression of the Ubiquitin Carboxyl Terminal Hydrolase L1 Gene in Human Airway Epithelium of Cigarette Smokers The microarray data deposited here is from 39 HG-U133 Plus 2.0 GeneChips, from 12 normal non-smokers, 12 phenotypic normal smokers, 9 Early COPD and 6 COPD individuals, all small airways, all small airway. A subset of these samples have been already submitted under GEO Accession Number GSE 4498. These are: 12 non-smokers samples (GSM101095-GSM101106) and 10 smoker samples (GSM101107-GSM101116). These 22 samples that are also in GSE4498 were described in Harvey, B-G; Heguy, A.; Leopold, P.L.; Carolan, B.; Ferris, B. and Crystal R.G. Modification of Gene Expression of the Small Airway Epithelium in Response to Cigarette Smoking. J. Mol. Med (in press). These data are part of a study aimed at understanding how cigarette smoking modifies neuroendocrine cells, in which microarray analysis with TaqMan confirmation was used to assess airway epithelial samples obtained by fiberoptic bronchoscopy from 81 individuals (normal nonsmokers, normal smokers, smokers with early COPD and smokers with established COPD). Of 11 genes considered to be neuroendocrine cell-specific, only ubiquitin C-terminal hydrolase L1(UCHL1), a member of the ubiquitin proteasome pathway, was consistently upregulated in smokers compared to nonsmokers. Up-regulation of UCHL1 at the protein level was observed with immunohistochemistry of bronchial biopsies of smokers compared to nonsmokers. Interestingly, however, while UCHL1 expression was present only in neuroendocrine cells of the airway epithelium in nonsmokers, UCHL1 expression was also expressed in ciliated epithelial cells in smokers, an intriguing observation in light of recent observations that ciliated cells can are capable of transdifferentiating to other airway epithelium. In the context that UCHL1 is involved in the degradation of unwanted, misfolded or damaged proteins within the cell and is overexpressed in >50% of lung cancers, its overexpression in chronic smokers may represent an early event in the complex transformation from normal epithelium to overt malignancy. Keywords: non-smokers vs phenotypic normal smokers, smokers with early COPD, and smokers with COPD
2006-11-21 | GSE5058 | GEO
Project description:Global genome-wide sequencing analysis of RNA prepared from Cyp1b1-/-AC and Cyp1b1+/+AC was perfomed to gain additional insight into the cellular regulatory mechanisms impacted by Cyp1b1 expression
2020-02-12 | GSE145103 | GEO
Project description:ECL1_1173151: FLAG-IP, HEK293T transfected with pcDNA3.1 vector expressing N-term-3XFLAG tagged GFP
ECL1_1173152: FLAG-IP, HEK293T transfected with pcDNA3.1 vector expressing N-term-3XFLAG tagged GFP
ECL1_1173153: FLAG-IP, HEK293T transfected with pcDNA3.1 vector expressing N-term-3XFLAG tagged CYP1B1
ECL1_1173154: FLAG-IP, HEK293T transfected with pcDNA3.1 vector expressing N-term-3XFLAG tagged CYP1B1
ECL1_1173155: FLAG-IP, HEK293T transfected with pcDNA3.1 vector expressing N-term-3XFLAG tagged CYP1B1 and infected with C.burnetii NMII
ECL1_1173156: FLAG-IP, HEK293T transfected with pcDNA3.1 vector expressing N-term-3XFLAG tagged CYP1B1 and infected with C.burnetii NMII
2024-12-23 | MSV000096725 | MassIVE
Project description:Upregulation of Expression of the Ubiquitin Carboxyl Terminal Hydrolase L1 Gene in Human Airway Epithelium of Cigarette Smokers The microarray data deposited here is from 44 HuGeneFL GeneChips, from 9 normal non-smokers and 13 phenotypic normal smokers, large airways, 2 samples per individual, one from the right lung and one from the left lung. These samples were previously described in Hackett NR, Heguy A, Harvey BG, O'Connor TP, Luettich K, Flieder DB, Kaplan R, Crystal RG. Variability of antioxidant-related gene expression in the airway epithelium of cigarette smokers. Am J Respir Cell Mol Biol. 2003 29:331-43 and in Heguy A, Harvey BG, O'Connor TP, Hackett NR, Crystal RG. Sampling-dependent up-regulation of gene expression in sequential samples of human airway epithelial cells. Mol Med. 2003 9:200-8. These data are part of a study aimed at understanding how cigarette smoking modifies neuroendocrine cells, in which microarray analysis with TaqMan confirmation was used to assess airway epithelial samples obtained by fiberoptic bronchoscopy from 81 individuals (normal nonsmokers, normal smokers, smokers with early COPD and smokers with established COPD). Of 11 genes considered to be neuroendocrine cell-specific, only ubiquitin C-terminal hydrolase L1(UCHL1), a member of the ubiquitin proteasome pathway, was consistently upregulated in smokers compared to nonsmokers. Up-regulation of UCHL1 at the protein level was observed with immunohistochemistry of bronchial biopsies of smokers compared to nonsmokers. Interestingly, however, while UCHL1 expression was present only in neuroendocrine cells of the airway epithelium in nonsmokers, UCHL1 expression was also expressed in ciliated epithelial cells in smokers, an intriguing observation in light of recent observations that ciliated cells can are capable of transdifferentiating to other airway epithelium. In the context that UCHL1 is involved in the degradation of unwanted, misfolded or damaged proteins within the cell and is overexpressed in >50% of lung cancers, its overexpression in chronic smokers may represent an early event in the complex transformation from normal epithelium to overt malignancy. Keywords: smokers vs non-smokers
2006-11-21 | GSE5056 | GEO
Project description:Investigating the transcriptional changes in mouse livers exposed to low and high fat diets for 11 weeks. Determine what gene changes in the Cyp1b1 null livers may be contributing to prevention of increased adiposity when givin a high fat diet. Three Comparison experiment. Comparing wild-type low fat vs Cyp1b1 null low fat, wild-type high fat vs Cyp1b1 null high fat and low fat vs high in wild-type mice. Sample size is 3 per group. Limma analysis data provided in Series supplementary file (Normalized log2 ratio of (Cy3/Cy5) representing test group/control group).
2014-01-09 | E-GEOD-53910 | biostudies-arrayexpress