A microRNA component of the p53 tumour suppressor network. Lin He, Xingyue He, Lee P. Lim, Elisa de Stanchina, Zhenyu Xuan, Yu Liang, Wen Xue, Lars Zender, Jill Magnus, Dana Ridzon, Aimee L. Jackson, Peter S. Linsley, Caifu Chen, Scott W. Lowe, Michele A. Cleary, and Gregory J. Hannon. Published in Nature, 2007. The study identifies miR-34a–c as a family of microRNAs regulated by p53, which are direct transcriptional targets of p53. These miRNAs are induced by DNA damage and oncogenic stress, and their expression reflects p53 status. Ectopic expression of miR-34 induces cell cycle arrest in various cell lines, consistent with their ability to downregulate genes promoting cell cycle progression. The p53 network suppresses tumour formation through the coordinated activation of multiple transcriptional targets, and miR-34 may act in concert with other effectors to inhibit inappropriate cell proliferation. miR-34s are evolutionarily conserved and belong to a family with orthologues in several invertebrate species. The miR-34 genes contain a region of significant sequence conservation in their promoter regions, which may be regulated by p53. Chromatin immunoprecipitation experiments show that p53 binds to the promoter regions of miR-34a and miR-34b/c. Reporter assays confirm that miR-34a and miR-34b/c are direct transcriptional targets of p53. miR-34s mediate growth arrest and apoptosis in various cell types, and their expression is regulated by p53. miR-34s also regulate cell cycle and DNA damage response genes, including cyclin E2, cyclin-dependent kinase 4, and the hepatocyte growth factor receptor. The study shows that miR-34s are direct targets of p53 and may mediate p53's tumour suppressor function. The miR-34 family is present in mammals and is also found in flies and worms, suggesting an evolutionary conserved role in p53 function. The study also highlights the importance of miR-34 in tumour suppression and its potential as a therapeutic target.A microRNA component of the p53 tumour suppressor network. Lin He, Xingyue He, Lee P. Lim, Elisa de Stanchina, Zhenyu Xuan, Yu Liang, Wen Xue, Lars Zender, Jill Magnus, Dana Ridzon, Aimee L. Jackson, Peter S. Linsley, Caifu Chen, Scott W. Lowe, Michele A. Cleary, and Gregory J. Hannon. Published in Nature, 2007. The study identifies miR-34a–c as a family of microRNAs regulated by p53, which are direct transcriptional targets of p53. These miRNAs are induced by DNA damage and oncogenic stress, and their expression reflects p53 status. Ectopic expression of miR-34 induces cell cycle arrest in various cell lines, consistent with their ability to downregulate genes promoting cell cycle progression. The p53 network suppresses tumour formation through the coordinated activation of multiple transcriptional targets, and miR-34 may act in concert with other effectors to inhibit inappropriate cell proliferation. miR-34s are evolutionarily conserved and belong to a family with orthologues in several invertebrate species. The miR-34 genes contain a region of significant sequence conservation in their promoter regions, which may be regulated by p53. Chromatin immunoprecipitation experiments show that p53 binds to the promoter regions of miR-34a and miR-34b/c. Reporter assays confirm that miR-34a and miR-34b/c are direct transcriptional targets of p53. miR-34s mediate growth arrest and apoptosis in various cell types, and their expression is regulated by p53. miR-34s also regulate cell cycle and DNA damage response genes, including cyclin E2, cyclin-dependent kinase 4, and the hepatocyte growth factor receptor. The study shows that miR-34s are direct targets of p53 and may mediate p53's tumour suppressor function. The miR-34 family is present in mammals and is also found in flies and worms, suggesting an evolutionary conserved role in p53 function. The study also highlights the importance of miR-34 in tumour suppression and its potential as a therapeutic target.