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Published on: January 7, 2019
Identification of novel Myc target genes with a potential role in lymphomagenesis
Dragan Marinkovic1, Tatjana Marinkovic, Eniko Kokai
1Department of Physiological Chemistry, University of Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
Abstract:
The c-Myc transcription factor regulates a wide set of genes involved in processes such as proliferation, differentiation and apoptosis. Therefore, altered expression of Myc leads to deregulation of a large number of target genes and, as a consequence, to tumorigenesis. For understanding Myc-induced transformation, identification of these target genes is essential. In this study, we searched for Myc target genes involved in lymphomagenesis using different mouse T and B cell lymphoma cell lines transformed by a conditional Myc-allele. Target genes obtained by microarray experiments were further subjected to a kinetic analysis of mRNA expression upon Myc inactivation/reactivation, bioinformatic examination of Myc binding sites and chromatin immunoprecipitation. This approach allowed us to define targets whose activation is a direct consequence of Myc binding. Among the 38 novel Myc targets, we identified several genes implicated in the tumor development. These genes are not only relevant for mouse lymphomas because we observed their upregulation in human lymphomas as well. Our findings further the understanding of Myc-induced lymphomagenesis and help toward developing more efficient antitumor strategies.
Insights
Researchers identified 38 new Myc target genes crucial for lymphomagenesis. These genes, involved in cell growth and death, are implicated in both mouse and human lymphomas, aiding in developing new cancer treatments.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- The c-Myc transcription factor controls genes essential for cell proliferation, differentiation, and apoptosis.
- Dysregulated Myc expression contributes to tumorigenesis by affecting numerous target genes.
- Identifying Myc target genes is critical for understanding Myc-induced transformation and developing targeted therapies.
Purpose of the Study:
- To identify novel Myc target genes involved in lymphomagenesis using mouse lymphoma cell lines.
- To validate direct Myc transcriptional regulation of identified target genes.
- To assess the relevance of identified Myc targets in human lymphomas.
Main Methods:
- Utilized conditional Myc-allele mouse T and B cell lymphoma lines.
- Performed microarray analysis to identify potential Myc target genes.
- Conducted kinetic mRNA expression analysis upon Myc inactivation/reactivation.
- Employed bioinformatic analysis of Myc binding sites and chromatin immunoprecipitation (ChIP) to confirm direct targets.
Main Results:
- Identified 38 novel Myc target genes.
- Confirmed direct Myc binding and transcriptional regulation for these targets.
- Several identified genes are implicated in tumor development.
- Observed upregulation of these genes in human lymphomas, indicating conserved roles.
Conclusions:
- This study elucidates key Myc target genes in lymphomagenesis.
- The findings highlight the conserved role of these genes in both mouse and human lymphomas.
- The identified genes offer potential targets for developing novel antitumor strategies against lymphomas.
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