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Genome-wide analysis reveals downregulation of miR-379/miR-656 cluster in human cancers

Saurabh V Laddha1, Subhashree Nayak, Deepanjan Paul

  • 1CSIR-Institute of Genomics & Integrative Biology, G,N, Ramachandran Knowledge Centre for Genome Informatics, Delhi, India.

Biology Direct
|April 27, 2013
PubMed
Abstract

Insights

The C14 miRNA cluster acts as a tumor suppressor, showing downregulation in multiple cancers like glioblastoma. This suggests coordinated function for clustered microRNAs in cancer development.

Area of Science:

  • Genomics
  • Cancer Biology
  • Molecular Oncology

Background:

  • MicroRNAs (miRNAs) are crucial gene regulators, with approximately 30% of human miRNAs organized in genomic clusters.
  • The imprinted miR-379/miR-656 cluster (C14) on chromosome 14q32.31 was selected to investigate the coordinated function of clustered miRNAs.

Purpose of the Study:

  • To analyze the expression profile of miRNAs within the C14 cluster across various human tissues and cancer types.
  • To determine the functional role of the C14 miRNA cluster in cancer, particularly glioblastoma multiforme (GBM).

Main Methods:

  • Expression profiling of over 1000 human miRNAs in more than 1400 cancer patient samples and controls.
  • Real-time PCR validation of miRNA downregulation in GBM samples.
  • Analysis of C14 locus methylation and transcription factor MEF2 expression in GBM.

Main Results:

  • Significant downregulation of C14 miRNAs observed in multiple cancers, including GBM (68%), kidney renal clear cell carcinoma (61%), and breast invasive carcinoma (46%).
  • C14 miRNAs accounted for 12-30% of total downregulated miRNAs across different cancers.
  • Pathway enrichment analysis identified significant involvement in cancer pathways, especially Glioma.
  • Downregulation in GBM was confirmed by real-time PCR (79% of C14 miRNAs).
  • Hypermethylation at the C14 locus and reduced MEF2 expression were observed in GBM, correlating with miRNA downregulation.

Conclusions:

  • The C14 miRNA cluster functions as a tumor suppressor locus implicated in various cancers, notably GBM.
  • Provides evidence for a general mechanism of coordinated function among clustered miRNAs in tumorigenesis.

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