The study investigates the role of the oncogenic transcription factor c-Myc in the repression of microRNA (miRNA) expression, which is a critical aspect of tumorigenesis. Through the analysis of human and mouse models of B cell lymphoma, the authors found that Myc regulates a broader set of miRNAs than previously known, with the predominant consequence being widespread repression of miRNA expression. Chromatin immunoprecipitation (ChIP) studies revealed that Myc binds directly to promoters or conserved regions upstream of the miRNAs it represses. The authors also showed that enforced expression of these repressed miRNAs impairs the growth of lymphoma cells in vivo, suggesting that repression of tumor-suppressing miRNAs is a key component of the Myc-mediated tumorigenic program. The findings highlight the importance of miRNA regulation in Myc-mediated tumorigenesis and suggest that restoring the expression of these miRNAs could be a therapeutic strategy for cancer.The study investigates the role of the oncogenic transcription factor c-Myc in the repression of microRNA (miRNA) expression, which is a critical aspect of tumorigenesis. Through the analysis of human and mouse models of B cell lymphoma, the authors found that Myc regulates a broader set of miRNAs than previously known, with the predominant consequence being widespread repression of miRNA expression. Chromatin immunoprecipitation (ChIP) studies revealed that Myc binds directly to promoters or conserved regions upstream of the miRNAs it represses. The authors also showed that enforced expression of these repressed miRNAs impairs the growth of lymphoma cells in vivo, suggesting that repression of tumor-suppressing miRNAs is a key component of the Myc-mediated tumorigenic program. The findings highlight the importance of miRNA regulation in Myc-mediated tumorigenesis and suggest that restoring the expression of these miRNAs could be a therapeutic strategy for cancer.