MicroRNA 125a and its regulation of the p53 tumor suppressor gene

MicroRNA (miRNA) are a class of non‐coding RNA that suppress gene expression by degradation or translational inhibition of target RNA. Several miRNA have been shown to target oncogenes and recently miRNA‐125b was shown to translationally and transcriptionally inhibit the p53 gene. Here, we show that an additional isomer of miRNA‐125 (miRNA‐125a) translationally arrests mRNA of the p53 tumor suppressor gene. The basis of this activity is the high degree of sequence homology between the seed sequence of miR‐125a and the 3′‐UTR of p53. Our findings add miRNA‐125a to the growing list of miRNA with oncogenic targets.

[1]  T. Tuschl,et al.  Mechanisms of gene silencing by double-stranded RNA , 2004, Nature.

[2]  F. Slack,et al.  Oncomirs — microRNAs with a role in cancer , 2006, Nature Reviews Cancer.

[3]  H. Lodish,et al.  MicroRNA-125b is a novel negative regulator of p53. , 2009, Genes & development.

[4]  V. Ambros,et al.  The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14 , 1993, Cell.

[5]  C. Croce,et al.  MicroRNA signatures in human ovarian cancer. , 2007, Cancer research.

[6]  George A Calin,et al.  MicroRNA signatures associated with cytogenetics and prognosis in acute myeloid leukemia. , 2008, Blood.

[7]  M. Svoboda,et al.  Micro-RNAs miR125b and miR137 are frequently upregulated in response to capecitabine chemoradiotherapy of rectal cancer. , 2008, International journal of oncology.

[8]  Yvonne Tay,et al.  A Pattern-Based Method for the Identification of MicroRNA Binding Sites and Their Corresponding Heteroduplexes , 2006, Cell.

[9]  Christopher P Evans,et al.  An androgen-regulated miRNA suppresses Bak1 expression and induces androgen-independent growth of prostate cancer cells , 2007, Proceedings of the National Academy of Sciences.

[10]  R. Stephens,et al.  Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. , 2006, Cancer cell.

[11]  C. Croce,et al.  A microRNA expression signature of human solid tumors defines cancer gene targets , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[12]  Jing Chen,et al.  Dissecting microregulation of a master regulatory network , 2008, BMC Genomics.

[13]  George A Calin,et al.  MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. , 2008, JAMA.

[14]  Sanghyuk Lee,et al.  MicroRNA genes are transcribed by RNA polymerase II , 2004, The EMBO journal.

[15]  Christopher M. Player,et al.  Large-Scale Sequencing Reveals 21U-RNAs and Additional MicroRNAs and Endogenous siRNAs in C. elegans , 2006, Cell.

[16]  N. Rajewsky,et al.  Widespread changes in protein synthesis induced by microRNAs , 2008, Nature.

[17]  R. Aharonov,et al.  Identification of hundreds of conserved and nonconserved human microRNAs , 2005, Nature Genetics.

[18]  Joel S Parker,et al.  Extensive post-transcriptional regulation of microRNAs and its implications for cancer. , 2006, Genes & development.

[19]  C. Croce,et al.  MicroRNA signatures in human cancers , 2006, Nature Reviews Cancer.

[20]  W. Filipowicz,et al.  Repression of protein synthesis by miRNAs: how many mechanisms? , 2007, Trends in cell biology.

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