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Identification of genes involved in cell invasion by using a library of randomized hybrid ribozymes.

ABSTRACT: Libraries of RNA helicase-coupled randomized ribozymes are a powerful tool for the identification of functional genes. We have demonstrated the usefulness of this functional gene-discovery system by identifying genes involved in tumor invasion, a process that is an essential feature of tumor metastasis: the spread of cancer cells from the original tumor to other sites in the body that imposes serious problems in the prognosis and treatment of cancer. Using a filter-based invasion assay in vitro, we isolated ribozymes that enhanced the invasive properties of NIH 3T3 fibroblasts. Sequence analysis of selected clones and a database search revealed that genes such as the gene for Gem GTPase and uncharacterized genes that resemble genes for myosin phosphatase and protein-tyrosine-phosphatase are involved in cell invasion. Our system for gene identification by using ribozymes and the functional analysis of target genes should help to clarify the complex mechanisms of invasion and metastasis and might provide information that is relevant to cancer therapy.

SUBMITTER: Suyama E

PROVIDER: S-EPMC156250 | biostudies-literature | 2003 May

REPOSITORIES: biostudies-literature

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Identification of genes involved in cell invasion by using a library of randomized hybrid ribozymes.

Suyama Eigo E Kawasaki Hiroaki H Nakajima Motowo M Taira Kazunari K

Proceedings of the National Academy of Sciences of the United States of America 20030428 10

Libraries of RNA helicase-coupled randomized ribozymes are a powerful tool for the identification of functional genes. We have demonstrated the usefulness of this functional gene-discovery system by identifying genes involved in tumor invasion, a process that is an essential feature of tumor metastasis: the spread of cancer cells from the original tumor to other sites in the body that imposes serious problems in the prognosis and treatment of cancer. Using a filter-based invasion assay in vitro, ...[more]

PMID: 12719525

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Project description:Alzheimer's disease (AD) is the leading cause of dementia worldwide, with recent studies highlighting the potential role of immunogenic cell death (ICD) in the pathogenesis of this neurodegenerative disorder. A total of 52 healthy controls and 64 patients with AD were included. Compared to the controls, the patients with AD exhibited 2392 differentially expressed genes (DEGs), of which 1015 and 1377 were upregulated and downregulated genes, respectively. Among them, nine common genes were identified by intersecting the AD-related module genes with the DEGs and ICD-associated genes. Gene ontology (GO)analysis further revealed "positive regulation of cytokine production" as the most significant term. Moreover, the enriched molecular functions were primarily related to the inflammatory body complex, while the overlapping genes were significantly enriched in lipopolysaccharide binding. Kyoto encyclopedia of genes and genomes (KEGG) analysis also indicated that these overlapping genes were mainly enriched in immunity, inflammation, and lipid metabolism pathways. Furthermore, the following four hub genes were detected using machine learning algorithms: P2RX7, HSP90AA1, NT5E, and NLRP3. These genes demonstrated significant differences in expression between the AD and healthy control groups (P < 0.05). Additionally, the area under the curve values of these four genes were all > 0.7, indicating their potential diagnostic value for AD. We further validated the protein levels of these four genes in the hippocampus of 3xTg-AD and C57BL/6J mice, showing P2RX7 and HSP90AA1 expression levels consistent with the previously analyzed trends. Finally, the single-sample gene set enrichment analysis (ssGSEA) algorithm provided additional evidence by demonstrating the crucial role of immune cell infiltration and its link with the hub genes in AD progression. Our study results suggest that ICD-mediated elevation of HSP90AA1 and P2RX7 levels and the resulting induction of tau hyperphosphorylation and neuroinflammation are vital in the AD pathogenic mechanism.

Dataset Information

Identification of genes involved in cell invasion by using a library of randomized hybrid ribozymes.

Publications

Identification of genes involved in cell invasion by using a library of randomized hybrid ribozymes.

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