The study investigates the role of microRNA (miRNA) *miR-145* in the posttranscriptional regulation of c-Myc by the tumor suppressor p53. The authors show that *miR-145* is expressed through the phosphoinositide-3 kinase (PI-3K)/Akt and p53 pathways. p53 transcriptionally induces *miR-145* by interacting with a potential p53 response element (p53RE) in the *miR-145* promoter. *miR-145* directly targets c-Myc, and its silencing by *miR-145* accounts for the inhibition of tumor cell growth both in vitro and in vivo. Additionally, the blockade of *miR-145* with anti-*miR-145* can reverse the p53-mediated repression of c-Myc. These findings suggest that *miR-145* plays a critical role in the posttranscriptional regulation of c-Myc by p53, providing a direct link between p53 and c-Myc in the gene regulatory network.The study investigates the role of microRNA (miRNA) *miR-145* in the posttranscriptional regulation of c-Myc by the tumor suppressor p53. The authors show that *miR-145* is expressed through the phosphoinositide-3 kinase (PI-3K)/Akt and p53 pathways. p53 transcriptionally induces *miR-145* by interacting with a potential p53 response element (p53RE) in the *miR-145* promoter. *miR-145* directly targets c-Myc, and its silencing by *miR-145* accounts for the inhibition of tumor cell growth both in vitro and in vivo. Additionally, the blockade of *miR-145* with anti-*miR-145* can reverse the p53-mediated repression of c-Myc. These findings suggest that *miR-145* plays a critical role in the posttranscriptional regulation of c-Myc by p53, providing a direct link between p53 and c-Myc in the gene regulatory network.