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miRNA Expression Analyses in Prostate Cancer Clinical Tissues
11:29

miRNA Expression Analyses in Prostate Cancer Clinical Tissues

Published on: September 8, 2015

Malignant germ cell tumors display common microRNA profiles resulting in global changes in expression of messenger

Roger D Palmer1, Matthew J Murray, Harpreet K Saini

  • 1Medical Research Council Cancer Cell Unit, Hills Road, Cambridge CB2 0XZ, United Kingdom.

Cancer Research
|March 25, 2010
PubMed

Insights

MicroRNAs from the miR-371-373 and miR-302 clusters are universally overexpressed in malignant germ cell tumors (GCT). These microRNAs coordinate the downregulation of messenger RNAs involved in significant biological pathways across GCT subtypes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Malignant germ cell tumors (GCT) exhibit clinical and pathological heterogeneity.
  • No common biological abnormalities have been identified in GCTs to date.
  • Primordial germ cells are the suspected origin of all malignant GCTs.

Purpose of the Study:

  • To identify common biological abnormalities in malignant germ cell tumors (GCT).
  • To investigate the role of microRNAs (miRNAs) in the pathogenesis of GCTs.
  • To determine if specific miRNA clusters are universally dysregulated in GCTs.

Main Methods:

  • Profiling of 615 microRNAs (miRNAs) in pediatric malignant GCTs, controls, and GCT cell lines.
  • Re-analysis of available miRNA expression data in adult gonadal malignant GCTs.
  • Application of the bioinformatic algorithm Sylamer to identify biologically significant miRNAs and their mRNA targets.

Main Results:

  • The miR-371-373 and miR-302 clusters were significantly overexpressed in malignant GCTs across all subtypes, sites, and ages.
  • Sylamer analysis identified a specific miRNA seed sequence (AAGUGC) complementary to a hexamer (GCACTT) enriched in the 3'-untranslated region of downregulated mRNAs.
  • Downregulated genes containing the GCACTT motif were significantly associated with cancer-associated processes, unlike those lacking the motif.

Conclusions:

  • The miR-371-373 and miR-302 clusters are universally overexpressed in malignant germ cell tumors (GCT).
  • These miRNA clusters coordinately downregulate messenger RNAs (mRNAs) involved in critical biological pathways.
  • This coordinated downregulation represents a common biological abnormality in malignant GCTs.

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