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

被引：51

作者：

Yu, Zuoren ^{[1
,2
,3
]}

Wang, Liping ^{[1
,2
]}

Wang, Chenguang ^{[1
,2
]}

Ju, Xiaoming ^{[1
,2
]}

Wang, Min ^{[1
,2
]}

Chen, Ke ^{[1
,2
]}

Loro, Emanuele ^{[1
,2
]}

Li, Zhiping ^{[1
,2
]}

Zhang, Yuzhen ^{[3
]}

Wu, Kongming ^{[1
,2
]}

Casimiro, Mathew C. ^{[1
,2
]}

Gormley, Michael ^{[1
,2
]}

Ertel, Adam ^{[1
,2
]}

Fortina, Paolo ^{[1
,2
]}

Chen, Yihan ^{[3
]}

Tozeren, Aydin ^{[2
,4
,5
]}

Liu, Zhongmin ^{[3
]}

Pestell, Richard G. ^{[1
,2
]}

机构：

[1] Thomas Jefferson Univ, Dept Canc Biol, Philadelphia, PA 19107 USA

[2] Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA

[3] Tongji Univ, Sch Med, East Hosp, Res Ctr Translat Med,Key Lab Basic Res Cardiol, Shanghai 200120, Peoples R China

[4] Drexel Univ, Ctr Integrated Bioinformat, Philadelphia, PA 19104 USA

[5] Drexel Univ, Sch Biomed Engn Syst & Hlth Sci, Philadelphia, PA 19104 USA

来源：

NATURE COMMUNICATIONS | 2013年 / 4卷

关键词：

REVEALS; BINDING; PROTEIN; BIOGENESIS; ACTIVATION; REPRESSION; MIGRATION; CELLS; P300; GENE;

D O I：

10.1038/ncomms3812

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Cyclin D1 encodes the regulatory subunit of a holoenzyme that phosphorylates the pRB protein and promotes G(1)/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.

引用

页数：10

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