Home LiteratureArticle Details
PMID: 20493775 Published · ppublish English Journal Article Review

Roles of small RNAs in tumor formation.

Trends in molecular medicine ·Vol. 16 ·No. 6 ·2010-06-00 ·Pages 257-67

Di Leva G, Croce CM

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs that act as post-transcriptional repressors of gene expression in organisms ranging from plants to humans. A widespread role for miRNAs in diverse molecular processes driving the initiation and progression of various tumor types has recently been described. Here, we discuss the etiology of the aberrant expression of miRNAs in human cancers and their role in tumor metastasis, which might define miRNAs as oncogenes or tumor suppressors. Moreover, we highlight the genomic/epigenetic alterations and transcriptional/post-transcriptional mechanisms associated with the misexpression of miRNAs in cancer. A better understanding of miRNA biology might ultimately yield further insight into the molecular mechanisms of tumorigenesis and new therapeutic strategies against cancer.

MeSH Terms
Animals Epigenesis, Genetic/genetics Humans MicroRNAs/genetics,metabolism Models, Biological Neoplasms/genetics
Chemicals
MicroRNAs
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Di Leva Gianpiero
Ohio State University Medical Center, Department of Molecular Virology, Immunology, and Medical Genetics, 460W 12th AVE, Columbus, OH 43210, USA.
Croce Carlo M
References (108)
108 references, click to expand
  1. Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation.
    Science. 2007 Mar 16;315(5818):1576-9 PMID: 17322030
  2. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis.
    Cancer Cell. 2006 Mar;9(3):189-98 PMID: 16530703
  3. Hypermethylation of let-7a-3 in epithelial ovarian cancer is associated with low insulin-like growth factor-II expression and favorable prognosis.
    Cancer Res. 2007 Nov 1;67(21):10117-22 PMID: 17974952
  4. Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in E(mu)-miR155 transgenic mice.
    Proc Natl Acad Sci U S A. 2006 May 2;103(18):7024-9 PMID: 16641092
  5. Hypoxia regulates TSC1/2-mTOR signaling and tumor suppression through REDD1-mediated 14-3-3 shuttling.
    Genes Dev. 2008 Jan 15;22(2):239-51 PMID: 18198340
  6. RNA polymerase III transcribes human microRNAs.
    Nat Struct Mol Biol. 2006 Dec;13(12):1097-101 PMID: 17099701
  7. Genomics of microRNA.
    Trends Genet. 2006 Mar;22(3):165-73 PMID: 16446010
  8. MicroRNA-dependent regulation of DNA methyltransferase-1 and tumor suppressor gene expression by interleukin-6 in human malignant cholangiocytes.
    Hepatology. 2010 Mar;51(3):881-90 PMID: 20146264
  9. Src homology 2 domain-containing inositol-5-phosphatase and CCAAT enhancer-binding protein beta are targeted by miR-155 in B cells of Emicro-MiR-155 transgenic mice.
    Blood. 2009 Aug 13;114(7):1374-82 PMID: 19520806
  10. miR-15 and miR-16 induce apoptosis by targeting BCL2.
    Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):13944-9 PMID: 16166262
  11. Sustained activation of ERK1/2 by NGF induces microRNA-221 and 222 in PC12 cells.
    FEBS J. 2009 Jun;276(12):3269-76 PMID: 19438724
  12. Selective blockade of microRNA processing by Lin28.
    Science. 2008 Apr 4;320(5872):97-100 PMID: 18292307
  13. Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation.
    EMBO J. 2007 Aug 8;26(15):3699-708 PMID: 17627278
  14. The human let-7a-3 locus contains an epigenetically regulated microRNA gene with oncogenic function.
    Cancer Res. 2007 Feb 15;67(4):1419-23 PMID: 17308078
  15. Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype?
    Nat Rev Cancer. 2007 Jun;7(6):415-28 PMID: 17508028
  16. Mir-17-5p regulates breast cancer cell proliferation by inhibiting translation of AIB1 mRNA.
    Mol Cell Biol. 2006 Nov;26(21):8191-201 PMID: 16940181
  17. Accumulation of miR-155 and BIC RNA in human B cell lymphomas.
    Proc Natl Acad Sci U S A. 2005 Mar 8;102(10):3627-32 PMID: 15738415
  18. MicroRNA gene expression deregulation in human breast cancer.
    Cancer Res. 2005 Aug 15;65(16):7065-70 PMID: 16103053
  19. Biogenesis of small RNAs in animals.
    Nat Rev Mol Cell Biol. 2009 Feb;10(2):126-39 PMID: 19165215
  20. MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias.
    Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11755-60 PMID: 15284443
  21. Modulation of microRNA processing by p53.
    Nature. 2009 Jul 23;460(7254):529-33 PMID: 19626115
  22. Genome-wide analysis of small RNA and novel MicroRNA discovery in human acute lymphoblastic leukemia based on extensive sequencing approach.
    PLoS One. 2009 Sep 02;4(9):e6849 PMID: 19724645
  23. Extensive modulation of a set of microRNAs in primary glioblastoma.
    Biochem Biophys Res Commun. 2005 Sep 9;334(4):1351-8 PMID: 16039986
  24. MicroRNA signatures associated with cytogenetics and prognosis in acute myeloid leukemia.
    Blood. 2008 Mar 15;111(6):3183-9 PMID: 18187662
  25. Correcting miR-15a/16 genetic defect in New Zealand Black mouse model of CLL enhances drug sensitivity.
    Mol Cancer Ther. 2009 Sep;8(9):2684-92 PMID: 19723889
  26. Monoallelic but not biallelic loss of Dicer1 promotes tumorigenesis in vivo.
    Cell Death Differ. 2010 Apr;17(4):633-41 PMID: 20019750
  27. Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes.
    Nat Immunol. 2008 Apr;9(4):405-14 PMID: 18327259
  28. Intronic microRNA precursors that bypass Drosha processing.
    Nature. 2007 Jul 5;448(7149):83-6 PMID: 17589500
  29. 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
  30. Karyotype-specific microRNA signature in chronic lymphocytic leukemia.
    Blood. 2009 Oct 29;114(18):3872-9 PMID: 19717645
  31. miR-221 overexpression contributes to liver tumorigenesis.
    Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):264-9 PMID: 20018759
  32. A microRNA polycistron as a potential human oncogene.
    Nature. 2005 Jun 9;435(7043):828-33 PMID: 15944707
  33. Impaired microRNA processing enhances cellular transformation and tumorigenesis.
    Nat Genet. 2007 May;39(5):673-7 PMID: 17401365
  34. Human colon cancer profiles show differential microRNA expression depending on mismatch repair status and are characteristic of undifferentiated proliferative states.
    BMC Cancer. 2009 Nov 18;9:401 PMID: 19922656
  35. Small non-coding RNAs in animal development.
    Nat Rev Mol Cell Biol. 2008 Mar;9(3):219-30 PMID: 18270516
  36. Morphogenesis in skin is governed by discrete sets of differentially expressed microRNAs.
    Nat Genet. 2006 Mar;38(3):356-62 PMID: 16462742
  37. The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited.
    Nat Rev Cancer. 2003 Jun;3(6):453-8 PMID: 12778135
  38. RAS is regulated by the let-7 microRNA family.
    Cell. 2005 Mar 11;120(5):635-47 PMID: 15766527
  39. MicroRNA cluster 221-222 and estrogen receptor alpha interactions in breast cancer.
    J Natl Cancer Inst. 2010 May 19;102(10):706-21 PMID: 20388878
  40. Complex networks orchestrate epithelial-mesenchymal transitions.
    Nat Rev Mol Cell Biol. 2006 Feb;7(2):131-42 PMID: 16493418
  41. Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA.
    Nature. 2000 Nov 2;408(6808):86-9 PMID: 11081512
  42. E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer.
    Cancer Cell. 2008 Mar;13(3):272-86 PMID: 18328430
  43. MicroRNA signatures in human ovarian cancer.
    Cancer Res. 2007 Sep 15;67(18):8699-707 PMID: 17875710
  44. Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters.
    Cell. 2008 Mar 7;132(5):875-86 PMID: 18329372
  45. 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
  46. Breaking news: high-speed race ends in arrest--how oncogenes induce senescence.
    Trends Cell Biol. 2007 Nov;17(11):529-36 PMID: 17980599
  47. Exploiting and antagonizing microRNA regulation for therapeutic and experimental applications.
    Nat Rev Genet. 2009 Aug;10(8):578-85 PMID: 19609263
  48. A restricted signature of miRNAs distinguishes APL blasts from normal promyelocytes.
    Oncogene. 2009 Nov 12;28(45):4034-40 PMID: 19749800
  49. 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
  50. E2F1-induced apoptosis: turning killers into therapeutics.
    Trends Mol Med. 2006 Apr;12(4):177-85 PMID: 16530485
  51. MicroRNA expression signatures in Barrett's esophagus and esophageal adenocarcinoma.
    Clin Cancer Res. 2009 Sep 15;15(18):5744-52 PMID: 19737949
  52. A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition.
    Cancer Res. 2008 Oct 1;68(19):7846-54 PMID: 18829540
  53. MicroRNAs regulate critical genes associated with multiple myeloma pathogenesis.
    Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):12885-90 PMID: 18728182
  54. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia.
    N Engl J Med. 2005 Oct 27;353(17):1793-801 PMID: 16251535
  55. The perfect storm of tiny RNAs.
    Nat Med. 2008 Oct;14(10):1041-5 PMID: 18841145
  56. Identification and characterization of a novel gene, C13orf25, as a target for 13q31-q32 amplification in malignant lymphoma.
    Cancer Res. 2004 May 1;64(9):3087-95 PMID: 15126345
  57. The promyelocytic leukemia zinc finger-microRNA-221/-222 pathway controls melanoma progression through multiple oncogenic mechanisms.
    Cancer Res. 2008 Apr 15;68(8):2745-54 PMID: 18417445
  58. Vascular endothelial growth factors are differentially regulated by steroid hormones and antiestrogens in breast cancer cells.
    Mol Cell Endocrinol. 1999 Mar 25;149(1-2):29-40 PMID: 10375015
  59. A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells.
    EMBO Rep. 2008 Jun;9(6):582-9 PMID: 18483486
  60. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2.
    Genes Dev. 2008 Apr 1;22(7):894-907 PMID: 18381893
  61. MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B.
    Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15805-10 PMID: 17890317
  62. Relation between microRNA expression and progression and prognosis of gastric cancer: a microRNA expression analysis.
    Lancet Oncol. 2010 Feb;11(2):136-46 PMID: 20022810
  63. Identification of a microRNA panel for clear-cell kidney cancer.
    Urology. 2010 Apr;75(4):835-41 PMID: 20035975
  64. c-Myc-regulated microRNAs modulate E2F1 expression.
    Nature. 2005 Jun 9;435(7043):839-43 PMID: 15944709
  65. 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
  66. MicroRNAs 221 and 222 bypass quiescence and compromise cell survival.
    Cancer Res. 2008 Apr 15;68(8):2773-80 PMID: 18413744
  67. MicroRNA signatures of TRAIL resistance in human non-small cell lung cancer.
    Oncogene. 2008 Jun 19;27(27):3845-55 PMID: 18246122
  68. A microRNA expression signature for cervical cancer prognosis.
    Cancer Res. 2010 Feb 15;70(4):1441-8 PMID: 20124485
  69. miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis.
    Nat Cell Biol. 2010 Mar;12(3):247-56 PMID: 20173740
  70. Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues.
    Oncogene. 2006 Apr 20;25(17):2537-45 PMID: 16331254
  71. Dicer1 functions as a haploinsufficient tumor suppressor.
    Genes Dev. 2009 Dec 1;23(23):2700-4 PMID: 19903759
  72. p53-independent upregulation of miR-34a during oncogene-induced senescence represses MYC.
    Cell Death Differ. 2010 Feb;17(2):236-45 PMID: 19696787
  73. MicroRNA expression profiles classify human cancers.
    Nature. 2005 Jun 9;435(7043):834-8 PMID: 15944708
  74. MicroRNA fingerprints during human megakaryocytopoiesis.
    Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):5078-83 PMID: 16549775
  75. TUT4 in concert with Lin28 suppresses microRNA biogenesis through pre-microRNA uridylation.
    Cell. 2009 Aug 21;138(4):696-708 PMID: 19703396
  76. The DLEU2/miR-15a/16-1 cluster controls B cell proliferation and its deletion leads to chronic lymphocytic leukemia.
    Cancer Cell. 2010 Jan 19;17(1):28-40 PMID: 20060366
  77. miR-19 is a key oncogenic component of mir-17-92.
    Genes Dev. 2009 Dec 15;23(24):2839-49 PMID: 20008935
  78. A TARBP2 mutation in human cancer impairs microRNA processing and DICER1 function.
    Nat Genet. 2009 Mar;41(3):365-70 PMID: 19219043
  79. Maturation of microRNA is hormonally regulated by a nuclear receptor.
    Mol Cell. 2009 Oct 23;36(2):340-7 PMID: 19854141
  80. Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia.
    Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15524-9 PMID: 12434020
  81. MiRNAs, epigenetics, and cancer.
    Mamm Genome. 2008 Aug;19(7-8):517-25 PMID: 18688563
  82. Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer.
    Proc Natl Acad Sci U S A. 2008 May 13;105(19):7004-9 PMID: 18458333
  83. The estrogen receptor-alpha-induced microRNA signature regulates itself and its transcriptional response.
    Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15732-7 PMID: 19706389
  84. Embryonic stem cell microRNAs: defining factors in induced pluripotent (iPS) and cancer (CSC) stem cells?
    Curr Stem Cell Res Ther. 2009 Sep;4(3):168-77 PMID: 19492978
  85. The let-7a microRNA protects from growth of lung carcinoma by suppression of k-Ras and c-Myc in nude mice.
    J Cancer Res Clin Oncol. 2010 Jul;136(7):1023-8 PMID: 20033209
  86. MicroRNA-29b induces global DNA hypomethylation and tumor suppressor gene reexpression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1.
    Blood. 2009 Jun 18;113(25):6411-8 PMID: 19211935
  87. High expression of precursor microRNA-155/BIC RNA in children with Burkitt lymphoma.
    Genes Chromosomes Cancer. 2004 Feb;39(2):167-9 PMID: 14695998
  88. MicroRNA signatures characterize diffuse large B-cell lymphomas and follicular lymphomas.
    Br J Haematol. 2008 Sep;142(5):732-44 PMID: 18537969
  89. MicroRNAs and chromosomal abnormalities in cancer cells.
    Oncogene. 2006 Oct 9;25(46):6202-10 PMID: 17028600
  90. Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model.
    Cell. 2009 Jun 12;137(6):1005-17 PMID: 19524505
  91. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1.
    Nat Cell Biol. 2008 May;10(5):593-601 PMID: 18376396
  92. The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities.
    Nat Med. 2008 Nov;14(11):1271-7 PMID: 18931683
  93. MicroRNAs 221 and 222 inhibit normal erythropoiesis and erythroleukemic cell growth via kit receptor down-modulation.
    Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):18081-6 PMID: 16330772
  94. MicroRNA expression signature of human sarcomas.
    Oncogene. 2008 Mar 27;27(14):2015-26 PMID: 17922033
  95. MicroRNA deregulation in human thyroid papillary carcinomas.
    Endocr Relat Cancer. 2006 Jun;13(2):497-508 PMID: 16728577
  96. Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells.
    Cancer Cell. 2006 Jun;9(6):435-43 PMID: 16766263
  97. Causes and consequences of microRNA dysregulation in cancer.
    Nat Rev Genet. 2009 Oct;10(10):704-14 PMID: 19763153
  98. Genetic and epigenetic silencing of microRNA-203 enhances ABL1 and BCR-ABL1 oncogene expression.
    Cancer Cell. 2008 Jun;13(6):496-506 PMID: 18538733
  99. Posttranscriptional regulation of miRNAs harboring conserved terminal loops.
    Mol Cell. 2008 Nov 7;32(3):383-93 PMID: 18995836
  100. The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2.
    J Biol Chem. 2008 May 30;283(22):14910-4 PMID: 18411277
  101. A microRNA component of the p53 tumour suppressor network.
    Nature. 2007 Jun 28;447(7148):1130-4 PMID: 17554337
  102. Genomic profiling of microRNAs in bladder cancer: miR-129 is associated with poor outcome and promotes cell death in vitro.
    Cancer Res. 2009 Jun 1;69(11):4851-60 PMID: 19487295
  103. Genetic dissection of the miR-17~92 cluster of microRNAs in Myc-induced B-cell lymphomas.
    Genes Dev. 2009 Dec 15;23(24):2806-11 PMID: 20008931
  104. Fragile and unstable chromosomes in cancer: causes and consequences.
    Trends Genet. 2001 Jun;17(6):339-45 PMID: 11377796
  105. miR-221&222 regulate TRAIL resistance and enhance tumorigenicity through PTEN and TIMP3 downregulation.
    Cancer Cell. 2009 Dec 8;16(6):498-509 PMID: 19962668
  106. Genetic unmasking of an epigenetically silenced microRNA in human cancer cells.
    Cancer Res. 2007 Feb 15;67(4):1424-9 PMID: 17308079
  107. MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior.
    J Clin Oncol. 2006 Oct 10;24(29):4677-84 PMID: 16966691
  108. MicroRNAs: genomics, biogenesis, mechanism, and function.
    Cell. 2004 Jan 23;116(2):281-97 PMID: 14744438
Article Info
Journal
Trends in molecular medicine
Abbr.
Trends Mol Med
ISSN
1471-499X
DOI
10.1016/j.molmed.2010.04.001
Published
2010-06-00
Epub
2010-00-20
Pages
257-67
Language
English
Region
England
NLM ID
100966035
PMCID
PMC2885513
Subset
IM
Grants
NCI NIH HHS · P01 CA129242 · United States
NCI NIH HHS · P01 CA129242-03 · United States
External Links
PubMed source DOI: 10.1016/j.molmed.2010.04.001 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