Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cyclin D1 governs microRNA processing in breast cancer

29.11.2013
Cyclin D1, a protein that helps push a replicating cell through the cell cycle also mediates the processing and generation of mature microRNA (miRNA), according to new research publishing November 29 in Nature Communications.

The research suggests that a protein strongly implicated in human cancer also governs the non-protein-coding genome. The non-coding genome, previously referred to as junk DNA, makes up most of the human genome, and unlike the coding genome, varies greatly between species.

"In addition to its role in regulating the cell cycle, cyclin D1 induces Dicer and thereby promotes the maturation of miRNA," says lead researcher Richard Pestell, M.D., Ph.D., Director of the Kimmel Cancer Center at Thomas Jefferson University and Chair of the Department of Cancer Biology. Dicer is a protein that converts inactive hairpin-structured microRNA precursors into their active single stranded form. "The work supports the idea that cancer-causing proteins like cyclin D1 may drive cancer progression in part via miRNA biogenesis."

Using antisense RNA, Dr. Pestell's group was the first to show that cyclin D1 drives mammary tumor growth in vivo. In prior work, they showed that cyclin D1 regulates the non coding genome, and that the non-coding genome, in turn, regulates expression of cyclin D1. Furthermore, the group showed that many cancer patients encode a form of cyclin D1 that evades negative feedback from the non coding genome. These attenuating feedback loops between the non coding and coding genome may be a common theme in cancer and other biological processes.

In the current study, the group sought to investigate the mechanism by which cyclin D1 regulates the biogenesis of non coding miRNA. Dr. Pestell and colleagues developed transgenic mice that could induce cyclin D1 expression in the breast and examined cells with cyclin D1 gene deleted. The researchers noticed that cells lacking cyclin D1 produced less of the miRNA-processing protein, Dicer, and therefore had reduced levels of mature miRNA.

The group also examined cells lacking Dicer, and noted many similarities between Dicer-lacking and cyclin D1-lacking cells, in addition to failure of miRNA processing, suggesting a deeper connection between these two processes.

In addition to the in vitro studies, the researchers also examined over 2,200 patient samples. They found that patients with the luminal A subtype of breast cancer had increased levels of expression of both cyclin D1 and Dicer. Luminal A subtype of breast cancer is the most common type and also has the best prognosis. The more aggressive basal-like subtype of breast cancers, however, exhibited lower levels of cyclin D1 and Dicer, which would in turn globally reduce the level of mature miRNA. Indeed, lower levels of miRNAs have been observed in a number of human cancers.

"By linking the decrease in miRNA levels to Dicer, we show that a global decrease in miRNA processing may be important in the initiation and progression of certain cancers," says first author, Zuoren Yu, Ph.D., who holds a joint appointment at Jefferson's Kimmel Cancer Center and Tongji University School of Medicine in Shanghai, China.

Because the cyclin D1 gene has been implicated in a variety of other human cancers these findings may have broad implications for processing of non coding RNA in human tumorigenesis.

The authors declare that they have no conflicts of interest.

This work was supported in part by NIH grants R01CA070896, R01CA075503, R01CA132115, R01CA107382, R01CA086072, grants 2012CB966800 from National Basic Research Program of China and 81172515 from NSFC, the Kimmel Cancer Center NIH Cancer Center Core grant P30CA056036, generous grants from the Dr. Ralph and Marian C. Falk Medical Research Trust and a grant from the Pennsylvania Department of Health.

For more information, contact Edyta Zielinska, (215) 955-5291, edyta.zielinska@jefferson.edu.

About Jefferson

Thomas Jefferson University (TJU), the largest freestanding academic medical center in Philadelphia, is nationally renowned for medical and health sciences education and innovative research. Founded in 1824, TJU includes Jefferson Medical College (JMC), one of the largest private medical schools in the country and ranked among the nation's best medical schools by U.S. News & World Report, and the Jefferson Schools of Nursing, Pharmacy, Health Professions, Population Health and the Graduate School of Biomedical Sciences. Jefferson University Physicians is TJU's multi-specialty physician practice consisting of the full-time faculty of JMC. Thomas Jefferson University partners with its clinical affiliate, Thomas Jefferson University Hospitals.

Article Reference: Z. Yu et al., "Cyclin D1 Induction of Dicer Governs MicroRNA Processing and Expression in Breast Cancer," Nat Commun, doi: 10.1038/ncomms3554, 2013.

Edyta Zielinska | EurekAlert!
Further information:
http://www.jefferson.edu

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>