The study investigates the role of microRNAs (miRNAs) in the p53 tumor suppressor network. It identifies a family of miRNAs, miR-34a–c, whose expression is regulated by p53. These miRNAs are direct transcriptional targets of p53 and are induced by DNA damage and oncogenic stress. Ectopic expression of miR-34a–c induces cell cycle arrest in various cell lines, suggesting their ability to downregulate genes promoting cell cycle progression. The p53 network suppresses tumor formation through the coordinated activation of multiple transcriptional targets, and miR-34 may act in concert with other effectors to inhibit inappropriate cell proliferation. The study also highlights the evolutionary conservation of miR-34 family members and their potential involvement in the p53 pathway across different species. Additionally, the authors demonstrate that miR-34s can mediate their anti-proliferative effects through additive or synergistic effects on multiple targets, and that their expression levels are low in human tumors and cancer cell lines, possibly due to frequent p53 mutations.The study investigates the role of microRNAs (miRNAs) in the p53 tumor suppressor network. It identifies a family of miRNAs, miR-34a–c, whose expression is regulated by p53. These miRNAs are direct transcriptional targets of p53 and are induced by DNA damage and oncogenic stress. Ectopic expression of miR-34a–c induces cell cycle arrest in various cell lines, suggesting their ability to downregulate genes promoting cell cycle progression. The p53 network suppresses tumor formation through the coordinated activation of multiple transcriptional targets, and miR-34 may act in concert with other effectors to inhibit inappropriate cell proliferation. The study also highlights the evolutionary conservation of miR-34 family members and their potential involvement in the p53 pathway across different species. Additionally, the authors demonstrate that miR-34s can mediate their anti-proliferative effects through additive or synergistic effects on multiple targets, and that their expression levels are low in human tumors and cancer cell lines, possibly due to frequent p53 mutations.