MicroRNAs as Prognostic Indicators and Therapeutic Targets: Potential Effect on Breast Cancer Management

The discovery of microRNAs (miRNA) as novel modulators of gene expression has resulted in a rapidly expanding repertoire of molecules in this family, as reflected in the concomitant expansion of scientific literature. MiRNAs are a category of naturally occurring RNA molecules that play important regulatory roles in plants and animals by targeting mRNAs for cleavage or translational repression. Characteristically, miRNAs are noncoding, single-stranded short (18-22 nucleotides) RNAs, features which possibly explain why they had not been intensively investigated until recently. Accumulating experimental evidence indicates that miRNAs play a pivotal role in many cellular functions via the regulation of gene expression. Furthermore, their dysregulation and/or mutation has been shown in carcinogenesis. We provide a brief review of miRNA biogenesis and discuss the technical challenges of modifying experimental techniques to facilitate the identification and characterization of these small RNAs. MiRNA function and their involvement in malignancy, particularly their putative role as oncogenes or tumor suppressors is also discussed, with a specific emphasis on breast cancer. Finally, we comment on the potential role of miRNAs in breast cancer management, particularly in improving current prognostic tools and achieving the goal of individualized cancer treatment.

[1]  Yi Wen Kong,et al.  How do microRNAs regulate gene expression? , 2008, Biochemical Society transactions.

[2]  N. Miller,et al.  O-7 Micro-RNA expression profiling in primary breast tumours , 2007 .

[3]  M. Kerin,et al.  Monocyte Chemotactic Protein-1 Secreted by Primary Breast Tumors Stimulates Migration of Mesenchymal Stem Cells , 2007, Clinical Cancer Research.

[4]  Ola Snøve,et al.  Epigenetics and MicroRNAs , 2007, Pediatric Research.

[5]  B. White,et al.  The Micro-Ribonucleic Acid (miRNA) miR-206 Targets the Human Estrogen Receptor-α (ERα) and Represses ERα Messenger RNA and Protein Expression in Breast Cancer Cell Lines , 2007 .

[6]  Petrus Tang,et al.  Intronic microRNA: discovery and biological implications. , 2007, DNA and cell biology.

[7]  Shuomin Zhu,et al.  miR-21-mediated tumor growth , 2007, Oncogene.

[8]  F. Slack,et al.  The evolution of animal microRNA function. , 2007, Current opinion in genetics & development.

[9]  C. Benz,et al.  Coordinate Suppression of ERBB2 and ERBB3 by Enforced Expression of Micro-RNA miR-125a or miR-125b* , 2007, Journal of Biological Chemistry.

[10]  H. Dressman,et al.  Genomic signatures to guide the use of chemotherapeutics , 2006, Nature Medicine.

[11]  Irving L Weissman,et al.  Cancer stem cells--perspectives on current status and future directions: AACR Workshop on cancer stem cells. , 2006, Cancer research.

[12]  Anwar Hossain,et al.  Mir-17-5p Regulates Breast Cancer Cell Proliferation by Inhibiting Translation of AIB1 mRNA , 2006, Molecular and Cellular Biology.

[13]  C. Benz,et al.  Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies , 2006, Molecular Cancer.

[14]  Peter A. Jones,et al.  Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells. , 2006, Cancer cell.

[15]  S. Kauppinen,et al.  LNA-modified oligonucleotides mediate specific inhibition of microRNA function. , 2006, Gene.

[16]  Vladimir Benes,et al.  A sensitive array for microRNA expression profiling (miChip) based on locked nucleic acids (LNA). , 2006, RNA.

[17]  K. Livak,et al.  Multiplexing RT-PCR for the detection of multiple miRNA species in small samples. , 2006, Biochemical and biophysical research communications.

[18]  J. Mattick,et al.  Non-coding RNA. , 2006, Human molecular genetics.

[19]  Anton J. Enright,et al.  Zebrafish MiR-430 Promotes Deadenylation and Clearance of Maternal mRNAs , 2006, Science.

[20]  Xiaowei Wang,et al.  Systematic identification of microRNA functions by combining target prediction and expression profiling , 2006, Nucleic acids research.

[21]  A. Jemal,et al.  Cancer Statistics, 2006 , 2006, CA: a cancer journal for clinicians.

[22]  Jin-Wu Nam,et al.  Genomics of microRNA. , 2006, Trends in genetics : TIG.

[23]  Jerry Pelletier,et al.  Short RNAs repress translation after initiation in mammalian cells. , 2006, Molecular cell.

[24]  Stijn van Dongen,et al.  miRBase: microRNA sequences, targets and gene nomenclature , 2005, Nucleic Acids Res..

[25]  Anwar Hossain,et al.  Mir-17-5 p Regulates Breast Cancer Cell Proliferation by Inhibiting Translation of AIB 1 mRNA , 2006 .

[26]  N. Rajewsky,et al.  Silencing of microRNAs in vivo with ‘antagomirs’ , 2005, Nature.

[27]  David I. K. Martin,et al.  MicroRNAs control translation initiation by inhibiting eukaryotic initiation factor 4E/cap and poly(A) tail function. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[28]  R. Shiekhattar,et al.  Human RISC Couples MicroRNA Biogenesis and Posttranscriptional Gene Silencing , 2005, Cell.

[29]  H. Horvitz,et al.  The let-7 MicroRNA family members mir-48, mir-84, and mir-241 function together to regulate developmental timing in Caenorhabditis elegans. , 2005, Developmental cell.

[30]  C. Croce,et al.  MicroRNA gene expression deregulation in human breast cancer. , 2005, Cancer research.

[31]  H. Ruohola-Baker,et al.  Stem cell division is regulated by the microRNA pathway , 2005, Nature.

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

[33]  Gregory J. Hannon,et al.  MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies , 2005, Nature Cell Biology.

[34]  Yoko Takahashi,et al.  Aberrant expression of HOX genes in human invasive breast carcinoma. , 2005, Oncology Report.

[35]  Phillip D Zamore,et al.  Perspective: machines for RNAi. , 2005, Genes & development.

[36]  Shridar Ganesan,et al.  Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. , 2005, Genes & development.

[37]  B. Patterson,et al.  Letter to the editor. , 2018, Journal of professional nursing : official journal of the American Association of Colleges of Nursing.

[38]  C. Burge,et al.  Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are MicroRNA Targets , 2005, Cell.

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

[40]  S. Moon,et al.  Human embryonic stem cells express a unique set of microRNAs. , 2004, Developmental biology.

[41]  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.

[42]  Thomas Tuschl,et al.  Sequence-specific inhibition of microRNA- and siRNA-induced RNA silencing. , 2004, RNA.

[43]  Phillip D Zamore,et al.  Sequence-Specific Inhibition of Small RNA Function , 2004, PLoS biology.

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

[45]  R. Plasterk,et al.  Substrate requirements for let-7 function in the developing zebrafish embryo. , 2004, Nucleic acids research.

[46]  S. Elledge,et al.  Dicer is essential for mouse development , 2003, Nature Genetics.

[47]  Martin Tabler,et al.  Developmental defects by antisense-mediated inactivation of micro-RNAs 2 and 13 in Drosophila and the identification of putative target genes. , 2003, Nucleic acids research.

[48]  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.

[49]  R. Tibshirani,et al.  Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[50]  G. Hampton,et al.  Definition and refinement of chromosome 11 regions of loss of heterozygosity in breast cancer: identification of a new region at 11q23.3. , 1995, Cancer research.

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