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PMID: 14973191 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 9 ·2004-03-02 ·Pages 2999-3004

Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M, Croce CM

Abstract

A large number of tiny noncoding RNAs have been cloned and named microRNAs (miRs). Recently, we have reported that miR-15a and miR-16a, located at 13q14, are frequently deleted and/or down-regulated in patients with B cell chronic lymphocytic leukemia, a disorder characterized by increased survival. To further investigate the possible involvement of miRs in human cancers on a genome-wide basis, we have mapped 186 miRs and compared their location to the location of previous reported nonrandom genetic alterations. Here, we show that miR genes are frequently located at fragile sites, as well as in minimal regions of loss of heterozygosity, minimal regions of amplification (minimal amplicons), or common breakpoint regions. Overall, 98 of 186 (52.5%) of miR genes are in cancer-associated genomic regions or in fragile sites. Moreover, by Northern blotting, we have shown that several miRs located in deleted regions have low levels of expression in cancer samples. These data provide a catalog of miR genes that may have roles in cancer and argue that the full complement of miRs in a genome may be extensively involved in cancers.

MeSH Terms
Chromosome Fragile Sites/genetics Chromosome Mapping Cloning, Molecular Databases, Nucleic Acid Genes, Homeobox Genetic Markers Genome, Human Humans Loss of Heterozygosity MicroRNAs/genetics Multigene Family Neoplasms/genetics PubMed
Chemicals
Genetic Markers MicroRNAs
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Calin George Adrian
Department of Microbiology and Immunology, Division of Clinical Pharmacology, Biostatistics Section, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Sevignani Cinzia
Dumitru Calin Dan
Hyslop Terry
Noch Evan
Yendamuri Sai
Shimizu Masayoshi
Rattan Sashi
Bullrich Florencia
Negrini Massimo
Croce Carlo M
References (48)
48 references, click to expand
  1. Homeobox genes and cancer.
    Exp Cell Res. 1999 Apr 10;248(1):1-9 PMID: 10094807
  2. Refinement of the LOH region 1 at 11q23.1 deleted in human breast carcinomas and sublocalization of 11 expressed sequence tags within the refined region.
    Oncogene. 1999 Feb 25;18(8):1635-8 PMID: 10102634
  3. Three new regions on chromosome 17p13.3 distal to p53 with possible tumor suppressor gene involvement in lung cancer.
    Jpn J Cancer Res. 2000 Jun;91(6):589-96 PMID: 10874210
  4. Evidence for 14 homeobox gene clusters in human genome ancestry.
    Curr Biol. 2000 Sep 7;10(17):1059-62 PMID: 10996074
  5. Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA.
    Nature. 2000 Nov 2;408(6808):86-9 PMID: 11081512
  6. Human papillomavirus type 16 integrations in cervical tumors frequently occur in common fragile sites.
    Cancer Res. 2000 Nov 1;60(21):5916-21 PMID: 11085503
  7. Fragile and unstable chromosomes in cancer: causes and consequences.
    Trends Genet. 2001 Jun;17(6):339-45 PMID: 11377796
  8. Wildtype Kras2 can inhibit lung carcinogenesis in mice.
    Nat Genet. 2001 Sep;29(1):25-33 PMID: 11528387
  9. WWOX: a candidate tumor suppressor gene involved in multiple tumor types.
    Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11417-22 PMID: 11572989
  10. Identification and characterization of human BIC, a gene on chromosome 21 that encodes a noncoding RNA.
    Gene. 2001 Aug 22;274(1-2):157-67 PMID: 11675008
  11. Identification of novel genes coding for small expressed RNAs.
    Science. 2001 Oct 26;294(5543):853-8 PMID: 11679670
  12. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans.
    Science. 2001 Oct 26;294(5543):858-62 PMID: 11679671
  13. An extensive class of small RNAs in Caenorhabditis elegans.
    Science. 2001 Oct 26;294(5543):862-4 PMID: 11679672
  14. Micro RNAs are complementary to 3' UTR sequence motifs that mediate negative post-transcriptional regulation.
    Nat Genet. 2002 Apr;30(4):363-4 PMID: 11896390
  15. miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs.
    Genes Dev. 2002 Mar 15;16(6):720-8 PMID: 11914277
  16. MicroRNAs: deviants no longer.
    Trends Genet. 2002 Apr;18(4):171-3 PMID: 11932009
  17. Identification of tissue-specific microRNAs from mouse.
    Curr Biol. 2002 Apr 30;12(9):735-9 PMID: 12007417
  18. A microRNA in a multiple-turnover RNAi enzyme complex.
    Science. 2002 Sep 20;297(5589):2056-60 PMID: 12154197
  19. HOX and non-HOX homeobox genes in leukemic hematopoiesis.
    Stem Cells. 2002;20(5):364-79 PMID: 12351808
  20. Tumor suppressor genes on chromosome 3p involved in the pathogenesis of lung and other cancers.
    Oncogene. 2002 Oct 7;21(45):6915-35 PMID: 12362274
  21. The Argonaute family: tentacles that reach into RNAi, developmental control, stem cell maintenance, and tumorigenesis.
    Genes Dev. 2002 Nov 1;16(21):2733-42 PMID: 12414724
  22. 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
  23. Systematic functional analysis of the Caenorhabditis elegans genome using RNAi.
    Nature. 2003 Jan 16;421(6920):231-7 PMID: 12529635
  24. Numerous microRNPs in neuronal cells containing novel microRNAs.
    RNA. 2003 Feb;9(2):180-6 PMID: 12554860
  25. MALT1 is deregulated by both chromosomal translocation and amplification in B-cell non-Hodgkin lymphoma.
    Blood. 2003 Jun 1;101(11):4539-46 PMID: 12560219
  26. The minimum LOH region defined on chromosome 17p13.3 in human hepatocellular carcinoma with gene content analysis.
    Cancer Lett. 2003 Feb 20;190(2):221-32 PMID: 12565177
  27. Common fragile sites are preferential targets for HPV16 integrations in cervical tumors.
    Oncogene. 2003 Feb 27;22(8):1225-37 PMID: 12606949
  28. Vertebrate microRNA genes.
    Science. 2003 Mar 7;299(5612):1540 PMID: 12624257
  29. bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila.
    Cell. 2003 Apr 4;113(1):25-36 PMID: 12679032
  30. Parkin, a gene implicated in autosomal recessive juvenile parkinsonism, is a candidate tumor suppressor gene on chromosome 6q25-q27.
    Proc Natl Acad Sci U S A. 2003 May 13;100(10):5956-61 PMID: 12719539
  31. The Drosophila microRNA Mir-14 suppresses cell death and is required for normal fat metabolism.
    Curr Biol. 2003 Apr 29;13(9):790-5 PMID: 12725740
  32. MicroRNA pathways in flies and worms: growth, death, fat, stress, and timing.
    Cell. 2003 Jun 13;113(6):673-6 PMID: 12809598
  33. Identification of eight members of the Argonaute family in the human genome.
    Genomics. 2003 Sep;82(3):323-30 PMID: 12906857
  34. Embryonic stem cell-specific MicroRNAs.
    Dev Cell. 2003 Aug;5(2):351-8 PMID: 12919684
  35. MicroRNAs: key participants in gene regulatory networks.
    Curr Opin Chem Biol. 2003 Aug;7(4):516-23 PMID: 12941428
  36. Common fragile sites.
    Cytogenet Genome Res. 2003;100(1-4):92-100 PMID: 14526169
  37. MicroRNAs and cancer.
    Semin Cancer Biol. 2003 Aug;13(4):253-8 PMID: 14563119
  38. Reduced accumulation of specific microRNAs in colorectal neoplasia.
    Mol Cancer Res. 2003 Oct;1(12):882-91 PMID: 14573789
  39. High expression of precursor microRNA-155/BIC RNA in children with Burkitt lymphoma.
    Genes Chromosomes Cancer. 2004 Feb;39(2):167-9 PMID: 14695998
  40. Oncogenes and tumor-suppressor genes - 2 different looks of the same gene.
    Oncol Rep. 1994 Sep;1(5):987-91 PMID: 21607481
  41. Fused transcripts of c-myc and a new cellular locus, hcr in a primary liver tumor.
    Oncogene. 1989 Jan;4(1):51-7 PMID: 2644611
  42. Activation of MYC in a masked t(8;17) translocation results in an aggressive B-cell leukemia.
    Proc Natl Acad Sci U S A. 1989 Nov;86(22):8867-71 PMID: 2682663
  43. Identification, molecular cloning, expression and chromosome mapping of a family of transformation upregulated hnRNP-K proteins derived by alternative splicing.
    J Mol Biol. 1994 Feb 11;236(1):33-48 PMID: 8107114
  44. The FHIT gene, spanning the chromosome 3p14.2 fragile site and renal carcinoma-associated t(3;8) breakpoint, is abnormal in digestive tract cancers.
    Cell. 1996 Feb 23;84(4):587-97 PMID: 8598045
  45. Diverse molecular interactions of the hnRNP K protein.
    FEBS Lett. 1997 Feb 17;403(2):113-5 PMID: 9042948
  46. Alterations of the PPP2R1B gene in human lung and colon cancer.
    Science. 1998 Oct 9;282(5387):284-7 PMID: 9765152
  47. Four tumor suppressor loci on chromosome 9q in bladder cancer: evidence for two novel candidate regions at 9q22.3 and 9q31.
    Oncogene. 1999 Jan 7;18(1):157-63 PMID: 9926930
  48. The role of the FHIT/FRA3B locus in cancer.
    Annu Rev Genet. 1998;32:7-31 PMID: 9928473
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0307323101
Published
2004-03-02
Epub
2004-00-18
Pages
2999-3004
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC365734
Subset
IM
Grants
NCI NIH HHS · P01CA56036 · United States
NCI NIH HHS · P01CA76259 · United States
NCI NIH HHS · P01 CA081534 · United States
NCI NIH HHS · P01 CA076259 · United States
NCI NIH HHS · P01CA81534 · United States
NCI NIH HHS · P30 CA056036 · United States
External Links
PubMed source DOI: 10.1073/pnas.0307323101 PMC Full Text View journal details
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