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miRNA Expression in Colon Polyps Provides Evidence for a Multihit Model of Colon Cancer

By Ann L. Oberg, Amy J. French, Aaron L. Sarver, Subbaya Subramanian, Bruce W. Morlan, Shaun M. Riska, Pedro M. Borralho, Julie M. Cunningham, Lisa A. Boardman, Liang Wang, Thomas C. Smyrk, Yan Asmann, Clifford J. Steer and Stephen N. Thibodeau

Abstract

Changes in miRNA expression are a common feature in colon cancer. Those changes occurring in the transition from normal to adenoma and from adenoma to carcinoma, however, have not been well defined. Additionally, miRNA changes among tumor subgroups of colon cancer have also not been adequately evaluated. In this study, we examined the global miRNA expression in 315 samples that included 52 normal colonic mucosa, 41 tubulovillous adenomas, 158 adenocarcinomas with proficient DNA mismatch repair (pMMR) selected for stage and age of onset, and 64 adenocarcinomas with defective DNA mismatch repair (dMMR) selected for sporadic (n = 53) and inherited colon cancer (n = 11). Sporadic dMMR tumors all had MLH1 inactivation due to promoter hypermethylation. Unsupervised PCA and cluster analysis demonstrated that normal colon tissue, adenomas, pMMR carcinomas and dMMR carcinomas were all clearly discernable. The majority of miRNAs that were differentially expressed between normal and polyp were also differentially expressed with a similar magnitude in the comparison of normal to both the pMMR and dMMR tumor groups, suggesting a stepwise progression for transformation from normal colon to carcinoma. Among the miRNAs demonstrating the largest fold up- or down-regulated changes (≥4), four novel (miR-31, miR-1, miR-9 and miR-99a) and two previously reported (miR-137 and miR-135b) miRNAs were identified in the normal/adenoma comparison. All but one of these (miR-99a) demonstrated similar expression differences in the two normal/carcinoma comparisons, suggesting that these early tumor changes are important in both the pMMR- and dMMR-derived cancers. The comparison between pMMR and dMMR tumors identified four miRNAs (miR-31, miR-552, miR-592 and miR-224) with statistically significant expression differences (≥2-fold change)

Topics: Research Article
Publisher: Public Library of Science
OAI identifier: oai:pubmedcentral.nih.gov:3111419
Provided by: PubMed Central

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Citations

  1. (2003). A comparison of normalization methods for high density oligonucleotide array data based on variance and bias.
  2. (2006). A genomewide map of aberrantly expressed chromosomal islands in colorectal cancer.
  3. (2004). A large imprinted microRNA gene cluster at the mouse Dlk1-Gtl2 domain.
  4. (1998). A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer.
  5. (2010). Aberrant silencing of imprinted genes on chromosome 12qFn mouse induced pluripotent stem cells.
  6. (2010). Alteration of microRNAs regulated by c-Myc in Burkitt lymphoma. PLoS One 5: pii:
  7. (2007). Altered expression of miR-21, miR-31, miR-143 and miR-145 is related to clinicopathologic features of colorectal cancer.
  8. (2004). An update on the genetics of colorectal cancer.
  9. (2010). Association of microRNA expression with microsatellite instability status in colorectal adenocarcinoma.
  10. (2005). Bioinformatics and computational biology solutions using R and bioconductor.
  11. (2009). Cancer statistics,
  12. (2009). Causes and consequences of microRNA dysregulation in cancer.
  13. (2006). Chromosomal instability in microsatellite-unstable and stable colon cancer.
  14. (1995). Controlling the false discovery rate: a practical and powerful approach to multiple testing.
  15. (2008). Core Team
  16. (2009). Deletion of Gtl2, imprinted non-coding RNA, with its differentially methylated region induces lethal parent-origin-dependent defects in mice.
  17. (2008). Diagnostic and prognostic microRNAs in stage II colon cancer.
  18. (2009). Differential expression of microRNA 181b and microRNA 21 in hyperplastic polyps and sessile serrated adenomas of the colon.
  19. (2010). DNA mismatch repair deficiency in sporadic colorectal cancer and Lynch syndrome.
  20. (2010). Epigenetic silencing of miR-137 is an early event in colorectal carcinogenesis.
  21. (2009). Evaluation of a new high-dimensional miRNA profiling platform.
  22. (2008). Exploration of tumorsuppressive microRNAs silenced by DNA hypermethylation in oral cancer.
  23. (2008). Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer.
  24. (2004). Genomic instability and colon cancer.
  25. (2010). Goel A
  26. (2008). Highly sensitive and specific microRNA expression profiling using BeadArray technology.
  27. (1937). Histological Grading of Rectal Cancer: (Section of Pathology).
  28. (2009). Human colon cancer profiles show differential microRNA expression depending on mismatch repair status and are characteristic of undifferentiated proliferative states.
  29. (1998). Hypermethylation of the hMLH1 promoter in colon cancer with microsatellite instability.
  30. (2006). Identification by Real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues.
  31. (2002). Immunohistochemistry versus microsatellite instability testing in phenotyping colorectal tumors.
  32. (2010). MicroRNA control of signal transduction.
  33. (2008). MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma.
  34. (2008). MicroRNA expression signature of human sarcomas.
  35. (2010). MicroRNA miR-183 functions as an oncogene by targeting the transcription factor EGR1 and promoting tumor cell migration.
  36. (2011). MicroRNAs and colon and rectal cancer: differential expression by tumor location and subtype.
  37. (2008). miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells.
  38. (2009). MiR-17-92 cluster is associated with 13q gain and c-myc expression during colorectal adenoma to adenocarcinoma progression.
  39. (2010). miR-31: A crucial overseer of tumor metastasis and other emerging roles.
  40. (2007). mRNA/ microRNA gene expression profile in microsatellite unstable colorectal cancer.
  41. (2005). Normalization of two-channel microarray experiments: a semiparametric approach.
  42. (2009). Overand under-expressed microRNAs in human colorectal cancer.
  43. (2008). PartekH Genomics Suite TM.
  44. (2007). Rabinovic A
  45. (2003). Reduced accumulation of specific microRNAs in colorectal neoplasia.
  46. (2008). Regulation of the adenomatous polyposis coli gene by the miR-135 family in colorectal cancer.
  47. (2010). S-MED: sarcoma microRNA expression database.
  48. (2003). Statistical significance for genomewide studies.
  49. (2005). Systematic review of microsatellite instability and colorectal cancer prognosis.
  50. (2002). The APC gene in colorectal cancer.
  51. (2001). The frequency of hereditary defective mismatch repair in a prospective series of unselected colorectal carcinomas.
  52. (2006). The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation.
  53. (2010). The widespread regulation of microRNA biogenesis, function and decay.
  54. (2005). Use of microsatellite instability and immunohistochemistry testing for the identification of individuals at risk for Lynch syndrome.