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Cyclin D1 induction of Dicer governs microRNA processing and expression in breast cancer.

Nature communications | 2013

Cyclin D1 encodes the regulatory subunit of a holoenzyme that phosphorylates the pRB protein and promotes G1/S cell-cycle progression and oncogenesis. Dicer is a central regulator of miRNA maturation, encoding an enzyme that cleaves double-stranded RNA or stem-loop-stem RNA into 20-25 nucleotide long small RNA, governing sequence-specific gene silencing and heterochromatin methylation. The mechanism by which the cell cycle directly controls the non-coding genome is poorly understood. Here we show that cyclin D1(-/-) cells are defective in pre-miRNA processing which is restored by cyclin D1a rescue. Cyclin D1 induces Dicer expression in vitro and in vivo. Dicer is transcriptionally targeted by cyclin D1, via a cdk-independent mechanism. Cyclin D1 and Dicer expression significantly correlates in luminal A and basal-like subtypes of human breast cancer. Cyclin D1 and Dicer maintain heterochromatic histone modification (Tri-m-H3K9). Cyclin D1-mediated cellular proliferation and migration is Dicer-dependent. We conclude that cyclin D1 induction of Dicer coordinates microRNA biogenesis.

Pubmed ID: 24287487 RIS Download

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Associated grants

  • Agency: NCI NIH HHS, United States
    Id: R01CA075503
  • Agency: NCI NIH HHS, United States
    Id: R01CA086072
  • Agency: NCI NIH HHS, United States
    Id: R01 CA070896
  • Agency: NCI NIH HHS, United States
    Id: R01CA132115
  • Agency: NCI NIH HHS, United States
    Id: P30CA056036
  • Agency: NCI NIH HHS, United States
    Id: R01CA107382
  • Agency: NCI NIH HHS, United States
    Id: R01 CA086072
  • Agency: NCI NIH HHS, United States
    Id: P30 CA056036
  • Agency: NCI NIH HHS, United States
    Id: R01 CA075503
  • Agency: NCI NIH HHS, United States
    Id: R01CA070896
  • Agency: NCI NIH HHS, United States
    Id: R01 CA132115
  • Agency: NCI NIH HHS, United States
    Id: R01 CA107382

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RRID:SCR_002964

International functional genomics data collection generated from microarray or next-generation sequencing (NGS) platforms. Repository of functional genomics data supporting publications. Provides genes expression data for reuse to the research community where they can be queried and downloaded. Integrated with the Gene Expression Atlas and the sequence databases at the European Bioinformatics Institute. Contains a subset of curated and re-annotated Archive data which can be queried for individual gene expression under different biological conditions across experiments. Data collected to MIAME and MINSEQE standards. Data are submitted by users or are imported directly from the NCBI Gene Expression Omnibus.

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RRID:SCR_007303

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