Novel c-MYC target genes mediate differential effects on cell proliferation and migration
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Updated: Jul 18, 2026

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
David Cappellen1, Thomas Schlange, Matthieu Bauer
1Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland. cappellen@igr.fr
Abstract:
The developmental and oncogenic roles of MYC proteins are well established, but the transcriptional targets mediating their functions remain elusive. Using small interfering RNA-mediated knockdown in breast and cervix carcinoma cell lines, which overexpress c-MYC, we show that c-MYC independently controls metabolism and cell proliferation, and can, depending on the cells, promote or inhibit migration. We identified new c-MYC target genes in these cell lines, and show that selective regulation of some targets correlates with the phenotypic responses of these different cell lines to c-MYC depletion. Notably, we show that a positive regulation of the WNT signalling pathway contributes to c-MYC pro-mitogenic effects in breast and cervix carcinoma cells. We also show that repression of CCL5/RANTES accounts for c-MYC anti-migratory effects in specific breast cancer cells. Our combined genomic and phenotypic analysis indicates that c-MYC functions are cellular-context-dependent and that selectively regulated genes are responsible for its differential properties.
Insights
The MYC protein
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- The roles of MYC proteins in development and cancer are known, but the specific genes they regulate are not fully understood.
- MYC proteins are crucial regulators of cell growth, proliferation, and metabolism.
Purpose of the Study:
- To identify novel c-MYC target genes in breast and cervix carcinoma cell lines.
- To investigate how c-MYC regulates cell metabolism, proliferation, and migration.
- To understand the cellular-context-dependent functions of c-MYC.
Main Methods:
- Small interfering RNA (siRNA)-mediated knockdown of c-MYC in carcinoma cell lines.
- Genomic and phenotypic analyses to identify c-MYC target genes and their functional impact.
- Analysis of WNT signaling pathway and CCL5/RANTES gene expression.
Main Results:
- c-MYC independently controls metabolism and proliferation, and differentially affects cell migration.
- New c-MYC target genes were identified, with selective regulation correlating to phenotypic changes.
- Upregulation of WNT signaling contributes to c-MYC's pro-mitogenic effects, while repression of CCL5/RANTES mediates anti-migratory effects in specific contexts.
Conclusions:
- c-MYC's functions are highly dependent on the cellular context.
- Specific target gene regulation explains the diverse roles of c-MYC in cancer cell behavior.
- Understanding context-specific MYC targets is crucial for developing targeted cancer therapies.
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