Home LiteratureArticle Details
PMID: 19721809 Published · ppublish English Journal Article

MicroRNA Gene Networks in Oncogenesis.

Current genomics ·Vol. 10 ·No. 1 ·2009-03-00 ·Pages 35-41

Drakaki A, Iliopoulos D

Abstract

MicroRNAs are small non-coding RNAs that regulate gene expression at the transcriptional or posttranscriptional level. They are involved in cellular development, differentiation, proliferation and apoptosis and play a significant role in cancer. Examination of tumor-specific microRNA expression profiles has revealed widespread deregulation of these molecules in diverse cancers. Several studies have shown that microRNAs function either as tumor suppressor genes or oncogenes, whose loss or overexpression respectively has diagnostic and prognostic significance. It seems that microRNAs act as major regulators of gene expression. In this review, we discuss microRNAs' role in cancer and how microRNAs exert their functions through regulation of their gene targets. Bioinformatic analysis of putative miRNA binding sites has indicated several novel potential gene targets involved in apoptosis, angiogenesis and metastatic mechanisms. Matching computational prediction analysis together with microarray data seems the best method for microRNA gene target identification. MicroRNAs together with transcription factors generate a complex combinatorial code regulating gene expression. Thus, manipulation of microRNA-transcription factor gene networks may be provides a novel approach for developing cancer therapies.

Keywords
carcinogenesis. gene networks gene regulation microRNAs
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Drakaki Alexandra
Caritas St Elizabeth Medical Center, Tufts University, Boston, MA, USA.
Iliopoulos Dimitrios
References (71)
71 references, click to expand
  1. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans.
    Nature. 2000 Feb 24;403(6772):901-6 PMID: 10706289
  2. Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model.
    Nat Genet. 2008 Jun;40(6):751-60 PMID: 18469815
  3. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis.
    Cancer Cell. 2006 Mar;9(3):189-98 PMID: 16530703
  4. Silencing of microRNAs in vivo with 'antagomirs'.
    Nature. 2005 Dec 1;438(7068):685-9 PMID: 16258535
  5. Dual role for argonautes in microRNA processing and posttranscriptional regulation of microRNA expression.
    Cell. 2007 Dec 14;131(6):1097-108 PMID: 18083100
  6. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets.
    Cell. 2005 Jan 14;120(1):15-20 PMID: 15652477
  7. MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma.
    JAMA. 2008 Jan 30;299(4):425-36 PMID: 18230780
  8. A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA.
    Science. 2001 Aug 3;293(5531):834-8 PMID: 11452083
  9. Combinatorial microRNA target predictions.
    Nat Genet. 2005 May;37(5):495-500 PMID: 15806104
  10. Computational analysis of miRNA-mediated repression of translation: implications for models of translation initiation inhibition.
    RNA. 2008 Aug;14(8):1480-91 PMID: 18579870
  11. RNAi-based drug discovery and its application to therapeutics.
    IDrugs. 2008 Apr;11(4):274-8 PMID: 18379962
  12. microRNAs and cancer: an overview.
    Cell Cycle. 2008 Aug 15;7(16):2485-92 PMID: 18719380
  13. A biochemical approach to identifying microRNA targets.
    Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19291-6 PMID: 18042700
  14. MicroRNA gene expression deregulation in human breast cancer.
    Cancer Res. 2005 Aug 15;65(16):7065-70 PMID: 16103053
  15. MicroRNAs: powerful new regulators of heart disease and provocative therapeutic targets.
    J Clin Invest. 2007 Sep;117(9):2369-76 PMID: 17786230
  16. Gene regulation by microRNAs.
    Curr Opin Genet Dev. 2006 Apr;16(2):203-8 PMID: 16503132
  17. microRNAs as oncogenes and tumor suppressors.
    Dev Biol. 2007 Feb 1;302(1):1-12 PMID: 16989803
  18. Human MicroRNA targets.
    PLoS Biol. 2004 Nov;2(11):e363 PMID: 15502875
  19. A combined computational-experimental approach predicts human microRNA targets.
    Genes Dev. 2004 May 15;18(10):1165-78 PMID: 15131085
  20. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers.
    Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):2999-3004 PMID: 14973191
  21. Reduced accumulation of specific microRNAs in colorectal neoplasia.
    Mol Cancer Res. 2003 Oct;1(12):882-91 PMID: 14573789
  22. The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2.
    Nat Med. 2007 Apr;13(4):486-91 PMID: 17401374
  23. Epstein-Barr virus microRNAs are evolutionarily conserved and differentially expressed.
    PLoS Pathog. 2006 Mar;2(3):e23 PMID: 16557291
  24. MicroRNAs as potential agents to alter resistance to cytotoxic anticancer therapy.
    Cancer Res. 2007 Dec 1;67(23):11111-6 PMID: 18056433
  25. microRNA target predictions in animals.
    Nat Genet. 2006 Jun;38 Suppl:S8-13 PMID: 16736023
  26. Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA.
    Nature. 2000 Nov 2;408(6808):86-9 PMID: 11081512
  27. MicroRNAs: a new class of gene regulators.
    Ann Med. 2008;40(3):197-208 PMID: 18382885
  28. A human cytomegalovirus-encoded microRNA regulates expression of multiple viral genes involved in replication.
    PLoS Pathog. 2007 Nov;3(11):e163 PMID: 17983268
  29. Identification of novel argonaute-associated proteins.
    Curr Biol. 2005 Dec 6;15(23):2149-55 PMID: 16289642
  30. Interferon modulation of cellular microRNAs as an antiviral mechanism.
    Nature. 2007 Oct 18;449(7164):919-22 PMID: 17943132
  31. A microRNA expression signature of human solid tumors defines cancer gene targets.
    Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2257-61 PMID: 16461460
  32. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival.
    Cancer Res. 2004 Jun 1;64(11):3753-6 PMID: 15172979
  33. A pancreatic islet-specific microRNA regulates insulin secretion.
    Nature. 2004 Nov 11;432(7014):226-30 PMID: 15538371
  34. How do microRNAs regulate gene expression?
    Sci STKE. 2007 Jan 02;2007(367):re1 PMID: 17200520
  35. Keeping quiet: microRNAs in HIV-1 latency.
    Nat Med. 2007 Oct;13(10):1138-40 PMID: 17917655
  36. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14.
    Cell. 1993 Dec 3;75(5):843-54 PMID: 8252621
  37. microRNAs and the regulation of glucose and lipid metabolism.
    Diabetes Obes Metab. 2007 Nov;9 Suppl 2:67-73 PMID: 17919180
  38. Chromatin decouples promoter threshold from dynamic range.
    Nature. 2008 May 8;453(7192):246-50 PMID: 18418379
  39. The let-7 MicroRNA family members mir-48, mir-84, and mir-241 function together to regulate developmental timing in Caenorhabditis elegans.
    Dev Cell. 2005 Sep;9(3):403-14 PMID: 16139228
  40. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans.
    Science. 2001 Oct 26;294(5543):858-62 PMID: 11679671
  41. c-Myc-regulated microRNAs modulate E2F1 expression.
    Nature. 2005 Jun 9;435(7043):839-43 PMID: 15944709
  42. Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis.
    Nucleic Acids Res. 2005 Mar 01;33(4):1290-7 PMID: 15741182
  43. Liver-specific microRNA miR-122 enhances the replication of hepatitis C virus in nonhepatic cells.
    J Virol. 2008 Aug;82(16):8215-23 PMID: 18550664
  44. MicroRNAs accurately identify cancer tissue origin.
    Nat Biotechnol. 2008 Apr;26(4):462-9 PMID: 18362881
  45. Widespread changes in protein synthesis induced by microRNAs.
    Nature. 2008 Sep 4;455(7209):58-63 PMID: 18668040
  46. Methods to analyze microRNA-mediated control of mRNA translation.
    Methods Enzymol. 2007;431:83-111 PMID: 17923232
  47. Loss of microRNA cluster miR-29a/b-1 in sporadic Alzheimer's disease correlates with increased BACE1/beta-secretase expression.
    Proc Natl Acad Sci U S A. 2008 Apr 29;105(17):6415-20 PMID: 18434550
  48. Systematic identification of microRNA functions by combining target prediction and expression profiling.
    Nucleic Acids Res. 2006 Mar 20;34(5):1646-52 PMID: 16549876
  49. MicroRNA expression profiles classify human cancers.
    Nature. 2005 Jun 9;435(7043):834-8 PMID: 15944708
  50. Dissecting microregulation of a master regulatory network.
    BMC Genomics. 2008 Feb 23;9:88 PMID: 18294391
  51. MicroRNA expression distinguishes between germinal center B cell-like and activated B cell-like subtypes of diffuse large B cell lymphoma.
    Int J Cancer. 2007 Sep 1;121(5):1156-61 PMID: 17487835
  52. Principles of microRNA-target recognition.
    PLoS Biol. 2005 Mar;3(3):e85 PMID: 15723116
  53. Prediction of mammalian microRNA targets.
    Cell. 2003 Dec 26;115(7):787-98 PMID: 14697198
  54. Non-coding RNAs in the nervous system.
    J Physiol. 2006 Sep 1;575(Pt 2):333-41 PMID: 16809366
  55. Functional integration of microRNAs into oncogenic and tumor suppressor pathways.
    Cell Cycle. 2008 Aug 15;7(16):2493-9 PMID: 18719378
  56. Switching from repression to activation: microRNAs can up-regulate translation.
    Science. 2007 Dec 21;318(5858):1931-4 PMID: 18048652
  57. The hallmarks of cancer.
    Cell. 2000 Jan 7;100(1):57-70 PMID: 10647931
  58. MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis.
    JAMA. 2007 May 2;297(17):1901-8 PMID: 17473300
  59. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting.
    Cell Metab. 2006 Feb;3(2):87-98 PMID: 16459310
  60. Sequence variants in SLITRK1 are associated with Tourette's syndrome.
    Science. 2005 Oct 14;310(5746):317-20 PMID: 16224024
  61. MicroRNA-133 controls cardiac hypertrophy.
    Nat Med. 2007 May;13(5):613-8 PMID: 17468766
  62. MicroTar: predicting microRNA targets from RNA duplexes.
    BMC Bioinformatics. 2006 Dec 18;7 Suppl 5:S20 PMID: 17254305
  63. MicroRNAs: new regulators of immune cell development and function.
    Nat Immunol. 2008 Aug;9(8):839-45 PMID: 18645592
  64. A microRNA mediates EGF receptor signaling and promotes photoreceptor differentiation in the Drosophila eye.
    Cell. 2005 Dec 29;123(7):1267-77 PMID: 16377567
  65. MicroRNAs direct rapid deadenylation of mRNA.
    Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):4034-9 PMID: 16495412
  66. Using expression profiling data to identify human microRNA targets.
    Nat Methods. 2007 Dec;4(12):1045-9 PMID: 18026111
  67. HBV-encoded microRNA candidate and its target.
    Comput Biol Chem. 2007 Apr;31(2):124-6 PMID: 17350341
  68. The utility of LNA in microRNA-based cancer diagnostics and therapeutics.
    Semin Cancer Biol. 2008 Apr;18(2):89-102 PMID: 18295505
  69. LNA-mediated microRNA silencing in non-human primates.
    Nature. 2008 Apr 17;452(7189):896-9 PMID: 18368051
  70. Substrate selectivity of exportin 5 and Dicer in the biogenesis of microRNAs.
    Cold Spring Harb Symp Quant Biol. 2006;71:59-66 PMID: 17381281
  71. The widespread impact of mammalian MicroRNAs on mRNA repression and evolution.
    Science. 2005 Dec 16;310(5755):1817-21 PMID: 16308420
Article Info
Journal
Current genomics
Abbr.
Curr Genomics
ISSN
1389-2029
DOI
10.2174/138920209787581299
Published
2009-03-00
Pages
35-41
Language
English
Region
United Arab Emirates
NLM ID
100960527
PMCID
PMC2699834
External Links
PubMed source DOI: 10.2174/138920209787581299 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2