Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer

Academic Article

Abstract

  • MicroRNAs (miRNAs) are an abundant class of small noncoding RNAs that function as negative gene regulators. miRNA deregulation is involved in the initiation and progression of human cancer; however, the underlying mechanism and its contributions to genome-wide transcriptional changes in cancer are still largely unknown. We studied miRNA deregulation in human epithelial ovarian cancer by integrative genomic approach, including miRNA microarray (n = 106), array-based comparative genomic hybridization (n = 109), cDNA microarray (n = 76), and tissue array (n = 504). miRNA expression is markedly down-regulated in malignant transformation and tumor progression. Genomic copy number loss and epigenetic silencing, respectively, may account for the downregulation of ≈15% and at least ≈36% of miRNAs in advanced ovarian tumors and miRNA down-regulation contributes to a genome-wide transcriptional deregulation. Last, eight miRNAs located in the chromosome 14 miRNA cluster (Dlk1-Gtl2 domain) were identified as potential tumor suppressor genes. Therefore, our results suggest that miRNAs may offer new biomarkers and therapeutic targets in epithelial ovarian cancer. © 2008 by The National Academy of Sciences of the USA.
  • Digital Object Identifier (doi)

    Author List

  • Zhang L; Volinia S; Bonome T; Calin GA; Greshock J; Yang N; Liu CG; Giannakakis A; Alexiou P; Hasegawa K
  • Start Page

  • 7004
  • End Page

  • 7009
  • Volume

  • 105
  • Issue

  • 19