Dataset Information

Transcriptomic Analyses Reveal Gene Expression Profiles and Networks in Nasopharyngeal Carcinoma.

ABSTRACT:

Background

Nasopharyngeal carcinoma (NPC) is a rare but highly aggressive tumor that is predominantly encountered in Southeast Asia and China in particular. Aside from radiotherapy, no effective therapy that specifically treats NPC is available, including targeted drugs. Finding more sensitive biomarkers is important for new drug discovery and for evaluating patient prognosis.

Methods

mRNA expression datasets from the Gene Expression Omnibus database (GSE53819, GSE64634, and GSE40290) were selected. After all samples in each dataset were subjected to quality control using principal component analyses, the qualified samples were used for additional analyses. The genes that were significantly expressed in each dataset were intersected to identify the most significant of these. Gene functional enrichment analyses were performed on these genes, using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses. The protein-protein interaction network of selected genes was analyzed using the Search Tool for the Retrieval of Interacting Genes database. Significantly, differentially expressed genes were further verified with two RNA-seq datasets (GSE68799 and GSE12452), as well as in clinical samples.

Results

In all, 34 (8 upregulated genes and 26 downregulated) genes were identified as significantly differentially expressed. The immune response and the regulation of cell proliferation were the most enriched biological GO terms. Using reverse transcription quantitative real-time PCR (RT-qPCR), the genes MMP1, AQP9, and TNFAIP6 were detected to be upregulated, and FAM3D, CR2, and LTF were downregulated in NPC tissue samples.

Conclusion

This study provides information on the genes that may be involved in the development of NPC and suggests possible druggable targets and biomarkers for diagnosing and evaluating the prognosis of NPC.

SUBMITTER: Zhou Y

PROVIDER: S-EPMC7850831 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Transcriptomic Analyses Reveal Gene Expression Profiles and Networks in Nasopharyngeal Carcinoma.

Zhou Yaqi Y Yang Weiqiang W Mei Xueshuang X Hu Hongyi H

BioMed research international 20210125

<h4>Background</h4>Nasopharyngeal carcinoma (NPC) is a rare but highly aggressive tumor that is predominantly encountered in Southeast Asia and China in particular. Aside from radiotherapy, no effective therapy that specifically treats NPC is available, including targeted drugs. Finding more sensitive biomarkers is important for new drug discovery and for evaluating patient prognosis.<h4>Methods</h4>mRNA expression datasets from the Gene Expression Omnibus database (GSE53819, GSE64634, and GSE40 ...[more]

PMID: 33564686

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Project description:Background:The transition to a more environmentally friendly economy has prompted studies of modern biorefineries, including the utilization of low-value lignocellulose. The major challenge facing the widespread application of biorefineries is the high cost of enzymes that can efficiently hydrolyze recalcitrant cellulose to sugars. Penicillium oxalicum produces large amounts of plant-cell-wall-degrading enzymes, but their production is tightly controlled by complex regulatory networks, resulting in low yields of the native enzymes. Regulatory genes have been the targets of genetic engineering to improve enzyme production in microorganisms. In this study, we used transcriptomic profiling and genetic analyses to screen for and identify novel key regulators of cellulase and xylanase gene expression in P. oxalicum. Results:A comparative analysis of the transcriptomes of P. oxalicum HP7-1 on different carbon sources, including glucose, wheat bran, and wheat bran plus Avicel, identified 40 candidate genes regulating the expression of cellulolytic enzyme genes. Deletion mutants of 31 candidate genes were constructed in P. oxalicum ∆PoxKu70 and 11 resultant mutants showed significant changes in their filter-paper cellulase production compared with the parental strain ∆PoxKu70. Among these 11 mutants, ΔPoxCxrA, ΔPoxCxrB, and ΔPoxNsdD showed the most significant reduction in the enzyme production (96.8, 75.9, and 58.5%, respectively). Ten of these 11 genes are here reported to be involved in cellulase production for the first time. Further tests revealed that ΔPoxCxrA, ΔPoxCxrB, and ΔPoxNsdD displayed significantly reduced xylanase production, whereas ΔPoxCxrA produced negligible xylanase. Interestingly, ΔPoxCxrB and ΔPoxNsdD showed significantly increased β-glucosidase production. Real-time quantitative reverse transcription-PCR and an electrophoretic mobility shift assay (EMSA) showed that PoxCxrA, PoxCxrB, and PoxNsdD regulate the expression of one another, but the mode of regulation changes dynamically during the growth of fungal cells in the presence of cellulose. EMSA showed that PoxCxrA, PoxCxrB, and PoxNsdD directly bind the putative promoters of major cellulase and xylanase genes. Conclusions:We have detected and identified three key new regulatory genes, PoxCxrA, PoxCxrB, and PoxNsdD, that directly and indirectly regulate the expression of cellulase and xylanase genes in P. oxalicum. This study provides novel insights into the regulatory mechanisms of fungal cellulase and xylanase gene expression.

Dataset Information

Transcriptomic Analyses Reveal Gene Expression Profiles and Networks in Nasopharyngeal Carcinoma.

Background

Methods

Results

Conclusion

Publications

Transcriptomic Analyses Reveal Gene Expression Profiles and Networks in Nasopharyngeal Carcinoma.

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