title: 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.affiliation: 1] Department of Cancer Biology, Thomas Jefferson University, 233 South 10th Street, Philadelphia, Pennsylvania 19107, USA [2] Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th Street, Philadelphia, Pennsylvania 19107, USA [3] Research Center for Translational Medicine, Key Laboratory for Basic Research in Cardiology, East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China.
authors.forename: Zuoren
authors.initials: Z
authors.lastname: Yu
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.forename: Chenguang
authors.initials: C
authors.lastname: Wang
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Ju
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Ke
authors.initials: K
authors.lastname: Chen
authors.forename: Emanuele
authors.initials: E
authors.lastname: Loro
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Li
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Zhang
authors.forename: Kongming
authors.initials: K
authors.lastname: Wu
authors.forename: Mathew C
authors.initials: MC
authors.lastname: Casimiro
authors.forename: Michael
authors.initials: M
authors.lastname: Gormley
authors.forename: Adam
authors.initials: A
authors.lastname: Ertel
authors.forename: Paolo
authors.initials: P
authors.lastname: Fortina
authors.forename: Yihan
authors.initials: Y
authors.lastname: Chen
authors.forename: Aydin
authors.initials: A
authors.lastname: Tozeren
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Liu
authors.forename: Richard G
authors.initials: RG
authors.lastname: Pestell
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000235:genetics; D043244:Ribonuclease III / Q000378:metabolism*
chemical_list: D006657:Histones; D035683:MicroRNAs; D019938:Cyclin D1; D043244:Ribonuclease III