The guardian's little helper: microRNAs in the p53 tumor suppressor network.

Several microRNAs (miRNAs) have been implicated in tumor development based on both changes in their expression patterns and gene structural alterations in human tumors. However, we are only now beginning to see how miRNAs interact with classic oncogene and tumor suppressor mechanisms. Several recent studies have implicated the miR-34 family of miRNAs in the p53 tumor suppressor network. The expression of miR-34a, miR-34b, and miR-34c is robustly induced by DNA damage and oncogenic stress in a p53-dependent manner. When overexpressed, miR-34 leads to apoptosis or cellular senescence, whereas reduction of miR-34 function attenuates p53-mediated cell death. These findings, together with the fact that miR-34 is down-regulated in several types of human cancer, show that miRNAs can affect tumorigenesis by working within the confines of well-known tumor suppressor pathways.

[1]  Ying Feng,et al.  Supplemental Data P53-mediated Activation of Mirna34 Candidate Tumor-suppressor Genes , 2022 .

[2]  R. Stallings,et al.  MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells , 2007, Oncogene.

[3]  V. Tarasov,et al.  Differential Regulation of microRNAs by p53 Revealed by Massively Parallel Sequencing: miR-34a is a p53 Target That Induces Apoptosis and G1-arrest , 2007, Cell cycle.

[4]  L. Lim,et al.  A microRNA component of the p53 tumour suppressor network , 2007, Nature.

[5]  Michael A. Beer,et al.  Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. , 2007, Molecular cell.

[6]  Moshe Oren,et al.  Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. , 2007, Molecular cell.

[7]  Anindya Dutta,et al.  The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. , 2007, Genes & development.

[8]  K. Coombes,et al.  Identification of Cell Cycle Regulatory Genes as Principal Targets of p53-mediated Transcriptional Repression* , 2006, Journal of Biological Chemistry.

[9]  A. Levine,et al.  The P53 pathway: what questions remain to be explored? , 2006, Cell Death and Differentiation.

[10]  Z. Weng,et al.  A Global Map of p53 Transcription-Factor Binding Sites in the Human Genome , 2006, Cell.

[11]  Phillip D. Zamore,et al.  Ribo-gnome: The Big World of Small RNAs , 2005, Science.

[12]  S. Lowe,et al.  A microRNA polycistron as a potential human oncogene , 2005, Nature.

[13]  H. Horvitz,et al.  MicroRNA expression profiles classify human cancers , 2005, Nature.

[14]  V. Ambros The functions of animal microRNAs , 2004, Nature.

[15]  C. Croce,et al.  Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[16]  D. Bartel MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[17]  Andreas Villunger,et al.  p53- and Drug-Induced Apoptotic Responses Mediated by BH3-Only Proteins Puma and Noxa , 2003, Science.

[18]  C. Croce,et al.  Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[19]  J. Levine,et al.  Surfing the p53 network , 2000, Nature.

[20]  James Brugarolas,et al.  Radiation-induced cell cycle arrest compromised by p21 deficiency , 1995, Nature.

[21]  Stephen J. Elledge,et al.  Mice Lacking p21 CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control , 1995, Cell.

[22]  John Calvin Reed,et al.  Tumor suppressor p53 is a direct transcriptional activator of the human bax gene , 1995, Cell.

[23]  B. Vogelstein,et al.  p53 mutations in human cancers. , 1991, Science.

[24]  David P. Bartel,et al.  Supporting Online Material Materials and Methods Fig. S1 Tables S1 and S2 References Database S1 Disrupting the Pairing between Let-7 and Hmga2 Enhances Oncogenic Transformation , 2022 .