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BACKGROUND: Oral squamous cell carcinoma (OSCC) severely affects the quality of life and the 5-year survival rate is low. Exploring the potential miRNA-mRNA regulatory network and analyzing hub genes and clinical data can provide a theoretical basis for further elucidating the pathogenesis of OSCC. METHODS: The miRNA expression datasets of GSE113956 and GSE124566 and mRNA expression datasets of GSE31056, GSE37991 and GSE13601 were obtained from the Gene Expression Omnibus databases. The differentially expressed miRNAs (DEMs) and mRNAs (DEGs) were screened using GEO2R. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by DAVID database. The PPI network was established through STRING database and the hub genes were preliminarily screened out by Cytoscape software. After identifying the hub genes in the TCGA database, we predicted the potential DEM transcription factors, constructed a miRNA-mRNA regulatory network, and analyzed the relationship between the hub genes and clinical data. RESULTS: A total of 28 DEMs and 764 DEGs were screened out, which were composed of 285 up-regulated genes and 479 down-regulated genes. Enrichment analysis showed that up-regulation of DEGs were mainly enriched in extracellular matrix organization and cancer-related pathway, while down-regulation of DEGs were mainly enriched in muscular system process and adrenaline signal transduction. After preliminary screening by PPI network and identification in TCGA, the up-regulated FN1, COL1A1, COL1A2, AURKA, CCNB1, CCNA2, SPP1, CDC6, and down-regulated ACTN2, TTN, IGF1, CAV3, MYL2, DMD, LDB3, CSRP3, ACTA1, PPARG were identified as hub genes. The miRNA-mRNA regulation network showed that hsa-miR-513b was the DEM with the most regulation, and COL1A1 was the DEG with the most regulation. In addition, CDC6, AURKA, CCNB1 and CCNA2 were related to overall survival and tumor differentiation. CONCLUSIONS: The regulatory relationship of hsa-miR-513b/ CDC6, CCNB1, CCNA2 and the regulatory relationship of hsa-miR-342-5p /AURKA were not only verified in the miRNA-mRNA regulatory network but also related to overall survival and tumor differentiation. These results indicated that they participated in the cellular regulatory process, and provided a molecular mechanism model for the study of pathogenesis.
- MeSH
- adrenalin MeSH
- aurora kinasa A genetika metabolismus MeSH
- dlaždicobuněčné karcinomy hlavy a krku * genetika MeSH
- genové regulační sítě MeSH
- kvalita života MeSH
- lidé MeSH
- messenger RNA genetika metabolismus MeSH
- mikro RNA * genetika MeSH
- nádory úst * genetika MeSH
- PPAR gama genetika metabolismus MeSH
- regulace genové exprese u nádorů MeSH
- stanovení celkové genové exprese MeSH
- transkripční faktory genetika MeSH
- výpočetní biologie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
In Saccharomyces cerevisiae, the Yap family of basic leucine zipper (bZip) proteins contains eight members. The Yap family proteins are implicated in a variety of stress responses; among these proteins, Yap1 acts as a major regulator of oxidative stress responses. However, the functional roles of the remaining Yap family members are poorly understood. To elucidate the function of Yap2, we mined candidate target genes of Yap2 by proteomic analysis. Among the identified genes, FRM2 was previously identified as a target gene of Yap2, which confirmed the validity of our screening method. YNL134C and YDL124W were also identified as candidate Yap2 target genes. These genes were upregulated in strains overexpressing Yap2 and possess Yap2 target sequences in their promoter regions. Furthermore, chromatin immunoprecipitation assays showed that YNL134C and YDL124W have Yap2 binding motif. These data will help to elucidate the functional role of Yap2.
- MeSH
- alkoholoxidoreduktasy biosyntéza genetika MeSH
- chromatinová imunoprecipitace MeSH
- DNA fungální genetika MeSH
- geny hub * MeSH
- oxidoreduktasy biosyntéza genetika MeSH
- promotorové oblasti (genetika) MeSH
- proteomika metody MeSH
- regulace genové exprese u hub * MeSH
- Saccharomyces cerevisiae - proteiny biosyntéza genetika metabolismus MeSH
- Saccharomyces cerevisiae genetika metabolismus MeSH
- transkripční faktory metabolismus MeSH
- vazba proteinů MeSH
- vazebná místa MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
For every eukaryotic cell to grow and divide, intricately coordinated action of numerous proteins is required to ensure proper cell-cycle progression. The fission yeast Schizosaccharomyces pombe has been instrumental in elucidating the fundamental principles of cell-cycle control. Mutations in S. pombe 'cut' (cell untimely torn) genes cause failed coordination between cell and nuclear division, resulting in catastrophic mitosis. Deletion of cbf11, a fission yeast CSL transcription factor gene, triggers a 'cut' phenotype, but the precise role of Cbf11 in promoting mitotic fidelity is not known. We report that Cbf11 directly activates the transcription of the acetyl-coenzyme A carboxylase gene cut6, and the biotin uptake/biosynthesis genes vht1 and bio2, with the former 2 implicated in mitotic fidelity. Cbf11 binds to a canonical, metazoan-like CSL response element (GTGGGAA) in the cut6 promoter. Expression of Cbf11 target genes shows apparent oscillations during the cell cycle using temperature-sensitive cdc25-22 and cdc10-M17 block-release experiments, but not with other synchronization methods. The penetrance of catastrophic mitosis in cbf11 and cut6 mutants is nutrient-dependent. We also show that drastic decrease in biotin availability arrests cell proliferation but does not cause mitotic defects. Taken together, our results raise the possibility that CSL proteins play conserved roles in regulating cell-cycle progression, and they could guide experiments into mitotic CSL functions in mammals.
- MeSH
- biotin metabolismus MeSH
- DNA fungální metabolismus MeSH
- genetická epistáze MeSH
- genetická transkripce MeSH
- geny hub * MeSH
- mitóza genetika MeSH
- mutace genetika MeSH
- promotorové oblasti (genetika) MeSH
- regulace genové exprese u hub * MeSH
- Schizosaccharomyces pombe - proteiny genetika metabolismus MeSH
- Schizosaccharomyces cytologie genetika MeSH
- vazba proteinů genetika MeSH
- Publikační typ
- časopisecké články MeSH
Cell cycle is controlled by the activity of protein family of cyclins and cyclin-dependent kinases that are periodically expressed during cell cycle and that are conserved among different species. Genome-wide location analysis found that cyclins are controlled by a small number of transcription factors that form closed network of genes controlling each other. To investigate gene expression dynamics of this network, we developed a general procedure for stochastic simulation of gene expression process. Using the binding data, we simulated gene expression of all genes of the network for all possible combinations of regulatory interactions and by statistical comparison with experimentally measured time series excluded those interactions that formed gene expression temporal profiles significantly different from the measured ones. These experiments led to a new definition of the cyclins regulatory network coherent with the binding experiments which are kinetically plausible. Level of influence of individual regulators in control of the regulated genes is defined. Simulation results indicate particular mechanism of regulatory activity of protein complexes involved in the control of cyclins.
A 3.85-kb genomic fragment containing the KlPCL1 gene, with an open reading frame (ORF) of 1359 bp, was isolated from Kluyveromyces lactis genomic library by heterologous colony hybridization using the Saccharomyces cerevisiae PRC1 (ScPRC1) gene as a probe. The KlPCL1 nucleotide sequence was identical to the KLLAOC17490g ORF of K. lactis and showed >55 % identity with S. cerevisiae YBR139w and PRC1 genes encoding carboxypeptidases. The deduced KlPcl1p amino acid sequence displayed strong similarities to yeast and higher eukaryotic carboxypeptidases. In silico analyses revealed that KlPcl1p contained several highly conserved regions characteristic of the serine-type carboxypeptidases, such as the catalytic triad in the active site and the LNGGPGCSS, FHIAGESYAGHYIP and ICNWLGN motifs involved in the substrate binding. All this suggests that the KlPCL1 gene product belongs to the serine carboxypeptidase family. Sporulation and ascus dissection of a diploid strain heterozygous for single-copy disruption of KlPCL1 revealed that this gene is not essential in K. lactis. Further analyses of haploid and diploid deletion mutants demonstrated that disruption of the KlPCL1 gene neither impaired sporulation nor affected growth abilities of K. lactis cells under a variety of physiological conditions, e.g., growth on different carbon sources, at various temperatures or pH of the medium, and under nitrogen depletion.
- MeSH
- fungální proteiny genetika chemie metabolismus MeSH
- karboxypeptidasy genetika chemie metabolismus MeSH
- klonování DNA MeSH
- Kluyveromyces enzymologie genetika chemie MeSH
- molekulární sekvence - údaje MeSH
- otevřené čtecí rámce MeSH
- regulace genové exprese u hub MeSH
- Saccharomyces cerevisiae - proteiny genetika metabolismus MeSH
- sekvence aminokyselin MeSH
- sekvenční seřazení MeSH
The transcription start points of the penicillin biosynthesis genes from Penicillium chrysogenum were mapped using the primer extension method. For each of the three genes consensus sequences of the core promoter elements were identified, supporting the notion that the basal transcription of these genes is mediated separately. Interestingly, transcription start of the pcbC gene is located within the potential Inr element with no TATA box-like sequence being found at expected position. This is in contrast to pcbAB and penDE genes with proposed TATA boxes or even to Aspergillus nidulans ipnA (pcbC) gene indicating possible differences in basal transcription regulation. Using the quantitative RT-PCR analysis the expression of all three biosynthesis genes was monitored in both the high and low production strain of P. chrysogenum during a 3-d cultivation under production conditions. The differences were found between the strains in time regulation and transcript levels of the biosynthesis genes. Furthermore, we showed that the effect of higher gene dosage on productivity in the production strain is amplified by more efficient transcription of the biosynthesis genes with the RNA levels approximately 37- and 12-times higher, respectively, than in a low production strain.
- MeSH
- financování organizované MeSH
- fungální proteiny genetika metabolismus MeSH
- molekulární sekvence - údaje MeSH
- peniciliny biosyntéza MeSH
- Penicillium chrysogenum genetika metabolismus MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- promotorové oblasti (genetika) MeSH
- regulace genové exprese u hub MeSH
- sekvence aminokyselin MeSH
- sekvence nukleotidů MeSH
During homologous recombination, Dbl2 protein is required for localisation of Fbh1, an F-box helicase that efficiently dismantles Rad51-DNA filaments. RNA-seq analysis of dbl2Δ transcriptome showed that the dbl2 deletion results in upregulation of more than 500 loci in Schizosaccharomyces pombe. Compared with the loci with no change in expression, the misregulated loci in dbl2Δ are closer to long terminal and long tandem repeats. Furthermore, the misregulated loci overlap with antisense transcripts, retrotransposons, meiotic genes and genes located in subtelomeric regions. A comparison of the expression profiles revealed that Dbl2 represses the same type of genes as the HIRA histone chaperone complex. Although dbl2 deletion does not alleviate centromeric or telomeric silencing, it suppresses the silencing defect at the outer centromere caused by deletion of hip1 and slm9 genes encoding subunits of the HIRA complex. Moreover, our analyses revealed that cells lacking dbl2 show a slight increase of nucleosomes at transcription start sites and increased levels of methylated histone H3 (H3K9me2) at centromeres, subtelomeres, rDNA regions and long terminal repeats. Finally, we show that other proteins involved in homologous recombination, such as Fbh1, Rad51, Mus81 and Rad54, participate in the same gene repression pathway.
- MeSH
- centromera MeSH
- histonový kód MeSH
- homologní rekombinace * MeSH
- nukleozomy metabolismus MeSH
- proteiny buněčného cyklu antagonisté a inhibitory metabolismus MeSH
- regulace genové exprese u hub * MeSH
- represorové proteiny fyziologie MeSH
- Schizosaccharomyces pombe - proteiny antagonisté a inhibitory metabolismus fyziologie MeSH
- Schizosaccharomyces genetika MeSH
- transkripční faktory antagonisté a inhibitory metabolismus MeSH
- umlčování genů * MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
