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Increased zinc finger protein zFOC1 transcripts in gastric cancer compared with normal gastric tissue.

ABSTRACT: BACKGROUND:Screening of cDNA arrays of the IMAGE library identified human zFOC1 as a differentially expressed cDNA that was upregulated in KATO III gastric cancer cells following stimulation with the gastric pathogen Helicobacter pylori. AIMS:To determine the expression of zFOC1 in gastric mucosa with and without H pylori infection and in patients with gastric cancer. RESULTS:zFOC1 is localised on chromosome 12q24.3 and encodes a zinc finger protein. Expression studies in human H pylori infected and uninfected gastric biopsies, gastric tumours, and gastric cancer cell lines revealed that zFOCI gene transcripts are significantly higher in gastric cancer than in non-cancerous gastric tissues. CONCLUSIONS:The zFOC1 gene appears to be a tumour marker associated with gastric cancer.

SUBMITTER: Stephen RL

PROVIDER: S-EPMC1187313 | biostudies-literature | 2003 Jun

REPOSITORIES: biostudies-literature

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Increased zinc finger protein zFOC1 transcripts in gastric cancer compared with normal gastric tissue.

Stephen R L RL Crabtree J E JE Yoshimura T T Clayton C L CL Dixon M F MF Robinson P A PA

Molecular pathology : MP 20030601 3

<h4>Background</h4>Screening of cDNA arrays of the IMAGE library identified human zFOC1 as a differentially expressed cDNA that was upregulated in KATO III gastric cancer cells following stimulation with the gastric pathogen Helicobacter pylori.<h4>Aims</h4>To determine the expression of zFOC1 in gastric mucosa with and without H pylori infection and in patients with gastric cancer.<h4>Results</h4>zFOC1 is localised on chromosome 12q24.3 and encodes a zinc finger protein. Expression studies in h ...[more]

PMID: 12782764

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Project description:ObjectiveThis study aims to investigate the expression, role, and detailed mechanism of microRNA-204-5p and zinc finger protein 521 in gastric cancer.MethodsImmunohistochemistry was adopted to detect the expressions of zinc finger protein 521 in 82 cases of gastric cancer tissues. Western blot was used to detect the expressions of zinc finger protein 521 in gastric cancer cells and adjacent cells. Moreover, the correlation between zinc finger protein 521 and the prognosis of patients were also evaluated. Cell Counting Kit 8 assay and colony formation assay were performed to figure out the impact of zinc finger protein 521 on the proliferation of gastric cancer cells. By conducting flow cytometry, the effect of zinc finger protein 521 on the apoptosis of gastric cancer cells was determined. The scratch wound healing assay and transwell invasion assay were carried out to determine the effect of zinc finger protein 521 on regulating the motility and invasion of gastric cancer cells. Ultimately, the targeting relationship and interaction between microRNA-204-5p and zinc finger protein 521 were verified by real-time polymerase chain reaction, Western blot, and dual luciferase reporter gene assay.ResultsCompared with adjacent cells, zinc finger protein 521 was highly expressed in gastric cancer cells, which was related to TNM stage (P = .0388), tumor size (P = .0168), and local lymph node metastasis (P = .0024). Overexpressed zinc finger protein 521 can promote the proliferation, migration, and invasion of gastric cancer cells and inhibit the apoptosis. Zinc finger protein 521 is a target gene of microRNA-106-5p, and there was a negative correlation between the expression of zinc finger protein 521 and microRNA-204-5p.ConclusionZinc finger protein 521 can arrest the apoptosis and enhance the proliferation, migration, and invasion of gastric cancer cells via regulating microRNA-204-5p. Our study may provide novel clues for the treatment of patients with gastric cancer.

Project description:Interferon-stimulated gene products (ISGs) play a crucial role in early infection control. The ISG zinc finger CCCH-type antiviral protein 1 (ZAP/ZC3HAV1) antagonizes several RNA viruses by binding to CG-rich RNA sequences, whereas its effect on DNA viruses is less well understood. Here, we decipher the role of ZAP in the context of human cytomegalovirus (HCMV) infection, a β-herpesvirus that is associated with high morbidity in immunosuppressed individuals and newborns. We show that expression of the two major isoforms of ZAP, ZAP-S and ZAP-L, is induced during HCMV infection and that both negatively affect HCMV replication. Transcriptome and proteome analyses demonstrated that the expression of ZAP results in reduced viral mRNA and protein levels and decelerates the progression of HCMV infection. Metabolic RNA labeling combined with high-throughput sequencing (SLAM-seq) revealed that most of the gene expression changes late in infection result from the general attenuation of HCMV. Furthermore, at early stages of infection, ZAP restricts HCMV by destabilizing a distinct subset of viral mRNAs, particularly those from the previously uncharacterized UL4-UL6 HCMV gene locus. Through enhanced cross-linking immunoprecipitation and sequencing analysis (eCLIP-seq), we identified the transcripts expressed from this HCMV locus as the direct targets of ZAP. Moreover, our data show that ZAP preferentially recognizes not only CG, but also other cytosine-rich sequences, thereby expanding its target specificity. In summary, this report is the first to reveal direct targets of ZAP during HCMV infection, which strongly indicates that transcripts from the UL4-UL6 locus may play an important role for HCMV replication.IMPORTANCE Viral infections have a large impact on society, leading to major human and economic losses and even global instability. So far, many viral infections, including human cytomegalovirus (HCMV) infection, are treated with a small repertoire of drugs, often accompanied by the occurrence of resistant mutants. There is no licensed HCMV vaccine in sight to protect those most at risk, particularly immunocompromised individuals or pregnant women who might otherwise transmit the virus to the fetus. Thus, the identification of novel intervention strategies is urgently required. In this study, we show that ZAP decelerates the viral gene expression cascade, presumably by selectively handpicking a distinct set of viral transcripts for degradation. Our study illustrates the potent role of ZAP as an HCMV restriction factor and sheds light on a possible role for UL4 and/or UL5 early during infection, paving a new avenue for the exploration of potential targets for novel therapies.

Dataset Information

Increased zinc finger protein zFOC1 transcripts in gastric cancer compared with normal gastric tissue.

Publications

Increased zinc finger protein zFOC1 transcripts in gastric cancer compared with normal gastric tissue.

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