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

Abstract

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.

• Authors: Zuoren Yu, Liping Wang, Chenguang Wang, Xiaoming Ju, Min Wang, Ke Chen, Emanuele Loro, Zhiping Li, Yuzhen Zhang, Kongming Wu, Mathew C Casimiro, Michael Gormley, Adam Ertel, Paolo Fortina, Yihan Chen, Aydin Tozeren, Zhongmin Liu, Richard G Pestell
• Journal: Nature communications (Nat Commun) Vol. 4 Pg. 2812 ( 2013) ISSN: 2041-1723 [Electronic] England
• PMID: 24287487 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Histones
• MicroRNAs
• Cyclin D1
• Ribonuclease III

Topics

• Animals
• Breast Neoplasms (enzymology, genetics, metabolism)
• Cell Movement (genetics)
• Cell Proliferation
• Cyclin D1 (physiology)
• Female
• Gene Expression Regulation, Neoplastic
• HCT116 Cells
• Histones (metabolism)
• Humans
• MCF-7 Cells
• Mammary Neoplasms, Experimental (enzymology, genetics, metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• MicroRNAs (biosynthesis, genetics)
• Protein Processing, Post-Translational (genetics)
• Ribonuclease III (metabolism)